Xiaorong Lin, Anastasia P. Litvintseva, Kirsten Nielsen, Sweta Patel, Anna Floyd, Thomas G. Mitchell, ...
Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction...
Many Globally Isolated AD Hybrid Strains of Cryptococcus neoformans Originated in Africa (2007)
Anastasia P. Litvintseva, Xiaorong Lin, Irka Templeton, Joseph Heitman, Thomas G. Mitchell
Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations. Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of...
Coccidioides Immitis, Coccidioides Posadasii, James A. Fraser, Jason E. Stajich, Eric J. Tarcha, Garry T. Cole, ...
Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell...
Yen-Ping Hsueh, Alexander Idnurm, Joseph Heitman
Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and,...
Xiaorong Lin, Johnny C. Huang, Thomas G. Mitchell, Joseph Heitman
Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and...
Abstract Summary Cyclophilins (Enzyme Commission (EC) number 5.1.2.8) belong to a group of proteins that have peptidyl-prolyl cis-trans isomerase activity; such proteins are collectively known as...
Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom (2005)
Alexander Idnurm, Joseph Heitman
Two genes controlling light responses - BWC1 and BWC2 - were identified and shown to regulate development and virulence of the fungal pathogen Cryptococcus neoformans.
Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom (2005)
Alexander Idnurm, Joseph Heitman
Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered...
Convergent Evolution of Chromosomal Sex-Determining Regions in the Animal and Fungal Kingdoms (2004)
James A. Fraser, Stephanie Diezmann, Ryan L. Subaran, Andria Allen, Klaus B. Lengeler, Fred S. Dietrich, ...
A comparative genomic analysis of the sex determining region in fungi reveals a remarkable similarity between its evolution and the events which shaped mammalian sex chromosomes
Convergent Evolution of Chromosomal Sex-Determining Regions in the Animal and Fungal Kingdoms (2004)
James A. Fraser, Stephanie Diezmann, Ryan L. Subaran, Andria Allen, Klaus B. Lengeler, Fred S. Dietrich, ...
Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen...
Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms (2004)
Fraser, James A., Diezmann, Stephanie, Subaran, Ryan L., Allen, Andria, Lengeler, Klaus B., Dietrich, Fred S., ...
Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen...
Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms (2004)
Fraser, James A., Diezmann, Stephanie, Subaran, Ryan L., Allen, Andria, Lengeler, Klaus B., Dietrich, Fred S., ...
Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen...
Roberts,Richard J., Belfort,Marlene, Bestor,Timothy, Bhagwat,Ashok S., Bickle,Thomas A., Bitinaite,Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Roberts, Richard J, Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S, Bickle, Thomas A, Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Roberts, Richard J., Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S., Bickle, Thomas A., Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Roberts, Richard J, Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S, Bickle, Thomas A, Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Roberts, Richard J., Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S., Bickle, Thomas A., Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Alspaugh, J. Andrew, Pukkila-Worley, Read, Harashima, Toshiaki, Cavallo, Lora M., Funnell, Deanna L., Cox, Gary M., ...
The signaling molecule cyclic AMP (cAMP) is a ubiquitous second messenger that enables cells to detect and respond to extracellular signals. cAMP is generated by the enzyme adenylyl cyclase, which is...
Schein, Jacqueline E., Tangen, Kristin L., Chiu, Readman, Shin, Heesun, Lengeler, Klaus B., MacDonald, William Kim, ...
Schein, Jacqueline E., Tangen, Kristin L., Chiu, Readman, Shin, Heesun, Lengeler, Klaus B., MacDonald, William Kim, ...
The TOR signaling cascade regulates gene expression in response to nutrients (1999)
Cardenas, Maria E., Cutler, N. Shane, Lorenz, Michael C., Di Como, Charles J., Heitman, Joseph
Heitman, Joseph, Harashima, Toshiaki
The Neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein, neurofibromin, which is a Ras GTPase-activating protein (RasGAP) activity. Although the NF1 gene was identified over...
On the repair of DNA breaks and the specificity of the EcoRI restriction enzyme. (1989)
Thesis (Ph. D.)--Rockefeller University.
Cassettes of the fl intergenic region (1989)
Heitman, Joseph, Treisman, Jessica, Davis, Nicholas G., Russel, Marjorie
Characterization of Alcohol-induced Filamentous Growth in Saccharomyces cerevisiae
Lorenz, Michael C., Cutler, N. Shane, Heitman, Joseph
Diploid cells of the budding yeast Saccharomyces cerevisiae starved for nitrogen differentiate into a filamentous growth form. Poor carbon sources such as starches can also stimulate filamentation,...
Protection from nitrosative stress by yeast flavohemoglobin
Liu, Limin, Zeng, Ming, Hausladen, Alfred, Heitman, Joseph, Stamler, Jonathan S.
Yeast hemoglobin was discovered close to half a century ago, but its function has remained unknown. Herein, we report that this flavohemoglobin protects Saccharomyces cerevisiae from nitrosative...
Lengeler, Klaus B., Wang, Ping, Cox, Gary M., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving mating between haploid MATa and MATα cells. Here we describe the isolation of part of the MATa...
Dolinski, Kara, Muir, Scott, Cardenas, Maria, Heitman, Joseph
The cyclophilins and FK506 binding proteins (FKBPs) bind to cyclosporin A, FK506, and rapamycin and mediate their immunosuppressive and toxic effects, but the physiological functions of these...
Alarcon, Clara M., Heitman, Joseph, Cardenas, Maria E.
In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle...
Dolinski, Kara, Scholz, Christian, Muir, R. Scott, Rospert, Sabine, Schmid, Franz X., Cardenas, Maria E., ...
Cyclophilin and FK506 binding protein (FKBP) accelerate cis–trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal...
The TOR Signal Transduction Cascade Controls Cellular Differentiation in Response to Nutrients
Cutler, N. Shane, Pan, Xuewen, Heitman, Joseph, Cardenas, Maria E.
Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In...
In response to nitrogen starvation, diploid cells of the yeast Saccharomyces cerevisiae differentiate to a filamentous growth form known as pseudohyphal differentiation. Filamentous growth is...
The G-Protein β Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans
Wang, Ping, Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle. The gene encoding a heterotrimeric G-protein β subunit, GPB1, was cloned and disrupted. gpb1 mutant strains...
D'Souza, Cletus A., Alspaugh, J. Andrew, Yue, Changli, Harashima, Toshiaki, Cox, Gary M., Perfect, John R., ...
Cryptococcus neoformans is an opportunistic fungal pathogen that infects the human central nervous system. This pathogen elaborates two specialized virulence factors: the antioxidant melanin and an...
Xue, Chaoyang, Bahn, Yong-Sun, Cox, Gary M., Heitman, Joseph
The Gα protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and...
Cardenas, Maria E., Cruz, M. Cristina, Del Poeta, Maurizio, Chung, Namjin, Perfect, John R., Heitman, Joseph
Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product...
Del Poeta, Maurizio, Chen, Shih-Fong, Von Hoff, Daniel, Dykstra, Christine C., Wani, Mansukh C., Manikumar, Govindarajan, ...
The activities of a series of camptothecin and nitidine derivatives that might interact with topoisomerase I were compared against yeast and cancer cell lines. Our findings reveal that structural...
Cruz, M. Cristina, Del Poeta, Maurizio, Wang, Ping, Wenger, Roland, Zenke, Gerhard, Quesniaux, Valerie F. J., ...
Cyclosporine (CsA) is an immunosuppressive and antimicrobial drug which, in complex with cyclophilin A, inhibits the protein phosphatase calcineurin. We recently found that Cryptococcus neoformans...
Del Poeta, Maurizio, Cruz, M. Cristina, Cardenas, Maria E., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system. Existing therapies include amphotericin B, fluconazole, and...
Cruz, M. Cristina, Goldstein, Alan L., Blankenship, Jill, Del Poeta, Maurizio, Perfect, John R., McCusker, John H., ...
Candida albicans and Cryptococcus neoformans cause both superficial and disseminated infections in humans. Current antifungal therapies for deep-seated infections are limited to amphotericin B,...
Del Poeta, Maurizio, Toffaletti, Dena L., Rude, Thomas H., Sparks, Sara D., Heitman, Joseph, Perfect, John R.
Synthetic green fluorescent protein (GFP) was used as a reporter to detect differential gene expression in the pathogenic fungus Cryptococcus neoformans. Promoters from the C. neoformans actin, GAL7,...
Cruz, M. Cristina, Sia, Rey A. L., Olson, Michael, Cox, Gary M., Heitman, Joseph
The calcineurin gene was cloned and disrupted in serotype D strains of Cryptococcus neoformans. Serotype A and serotype D calcineurin mutants were inviable at 37°C and avirulent in mice, whereas...
Lengeler, Klaus B., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a pathogenic basidiomycete with a defined sexual cycle involving mating between haploid yeast cells with a transient diploid state. C. neoformans occurs in four predominant...
Signal Transduction Cascades Regulating Fungal Development and Virulence
Lengeler, Klaus B., Davidson, Robert C., D'souza, Cletus, Harashima, Toshiaki, Shen, Wei-Chiang, Wang, Ping, ...
Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the...
In response to nitrogen limitation, Saccharomyces cerevisiae undergoes a dimorphic transition to filamentous pseudohyphal growth. In previous studies, the transcription factor Sok2 was found to...
Cruz, M. Cristina, Cavallo, Lora M., Görlach, Jenifer M., Cox, Gary, Perfect, John R., Cardenas, Maria E., ...
Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug...
Zaragoza, Dean, Ghavidel, Ataollah, Heitman, Joseph, Schultz, Michael C.
The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells...
Dolinski, Kara J., Cardenas, Maria E., Heitman, Joseph
Cyclophilins are cis-trans-peptidyl-prolyl isomerases that bind to and are inhibited by the immunosuppressant cyclosporin A (CsA). The toxic effects of CsA are mediated by the 18-kDa cyclophilin A...
Shen, Wei-Chiang, Davidson, Robert C., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATα and MATa cells. Interestingly, MATα strains are more common, are more virulent than congenic MATa...
Wang, Ping, Nichols, Connie B., Lengeler, Klaus B., Cardenas, Maria E., Cox, Gary M., Perfect, John R., ...
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATα and MATa cells. Virulence has been linked to the mating type, and MATα cells...
Alspaugh, J. Andrew, Pukkila-Worley, Read, Harashima, Toshiaki, Cavallo, Lora M., Funnell, Deanna, Cox, Gary M., ...
The signaling molecule cyclic AMP (cAMP) is a ubiquitous second messenger that enables cells to detect and respond to extracellular signals. cAMP is generated by the enzyme adenylyl cyclase, which is...
Calcineurin is essential for survival during membrane stress in Candida albicans
Cruz, M.Cristina, Goldstein, Alan L., Blankenship, Jill R., Del Poeta, Maurizio, Davis, Dana, Cardenas, Maria E., ...
The immunosuppressants cyclosporin A (CsA) and FK506 inhibit the protein phosphatase calcineurin and block T-cell activation and transplant rejection. Calcineurin is conserved in microorganisms and...
Mating-Type Locus of Cryptococcus neoformans: a Step in the Evolution of Sex Chromosomes
Lengeler, Klaus B., Fox, Deborah S., Fraser, James A., Allen, Andria, Forrester, Keri, Dietrich, Fred S., ...
The sexual development and virulence of the fungal pathogen Cryptococcus neoformans is controlled by a bipolar mating system determined by a single locus that exists in two alleles, α and a. The α...
Protein Kinase A Operates a Molecular Switch That Governs Yeast Pseudohyphal Differentiation
The yeast Saccharomyces cerevisiae undergoes a dimorphic filamentous transition in response to nutrient cues that is affected by both mitogen-activated protein kinase and cyclic AMP-protein kinase A...
Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis
Mylonakis, Eleftherios, Ausubel, Frederick M., Perfect, John R., Heitman, Joseph, Calderwood, Stephen B.
We found that the well-studied nematode Caenorhabditis elegans can use various yeasts, including Cryptococcus laurentii and Cryptococcus kuetzingii, as a sole source of food, producing similar brood...
Cruz, M.Cristina, Fox, Deborah S., Heitman, Joseph
Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+–...
Onyewu, Chiatogu, Blankenship, Jill R., Del Poeta, Maurizio, Heitman, Joseph
Azoles target the ergosterol biosynthetic enzyme lanosterol 14α-demethylase and are a widely applied class of antifungal agents because of their broad therapeutic window, wide spectrum of activity,...
Roberts, Richard J., Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S., Bickle, Thomas A., Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence
Blankenship, Jill R., Wormley, Floyd L., Boyce, Molly K., Schell, Wiley A., Filler, Scott G., Perfect, John R., ...
Calcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription...
Disruption of Ergosterol Biosynthesis Confers Resistance to Amphotericin B in Candida lusitaniae
Young, Laura Y., Hull, Christina M., Heitman, Joseph
Candida lusitaniae is an emerging human pathogen that, unlike other fungal pathogens, frequently develops resistance to the commonly used antifungal agent amphotericin B. Amphotericin B is a member...
Schein, Jacqueline E., Tangen, Kristin L., Chiu, Readman, Shin, Heesun, Lengeler, Klaus B., MacDonald, William Kim, ...
The basidiomycete fungus Cryptococcus neoformans is an important opportunistic pathogen of humans that poses a significant threat to immunocompromised individuals. Isolates of C. neoformans are...
Sexual Cycle of Cryptococcus neoformans var. grubii and Virulence of Congenic a and α Isolates
Nielsen, Kirsten, Cox, Gary M., Wang, Ping, Toffaletti, Dena L., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of...
Hull, Christina M., Davidson, Robert C., Heitman, Joseph
Virulence in the human fungal pathogen Cryptococcus neoformans is associated with the α mating type. Studies to identify the properties of α cells that enhance pathogenesis have led to the...
Fox, Deborah S., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. The Ca2+-calmodulin-activated protein phosphatase...
Fraser, James A., Subaran, Ryan L., Nichols, Connie B., Heitman, Joseph
Cryptococcus neoformans is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens C. neoformans var. neoformans (serotype D) and...
Görlach, Jenifer, Fox, Deborah S., Cutler, N.Shane, Cox, Gary M., Perfect, John R., Heitman, Joseph
Calcineurin is the conserved target of the immunosuppressants cyclosporin A and FK506. Using the yeast two-hybrid system, we identified a novel calcineurin binding protein, CBP1, from the pathogenic...
Wu, Xiaoyun, Wilcox, Cathy B., Devasahayam, Gina, Hackett, Robin L., Arévalo-Rodríguez, Miguel, Cardenas, Maria E., ...
The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by binding to cell cycle regulatory proteins and altering their activity. Here we isolate temperature-sensitive ess1...
Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3–Rpd3 histone deacetylase
Arévalo-Rodríguez, Miguel, Cardenas, Maria E., Wu, Xiaoyun, Hanes, Steven D., Heitman, Joseph
Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the...
Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP
Alspaugh, J. Andrew, Perfect, John R., Heitman, Joseph
This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogen Cryptococcus neoformans. The gene encoding a G-protein α...
The TOR signaling cascade regulates gene expression in response to nutrients
Cardenas, Maria E., Cutler, N. Shane, Lorenz, Michael C., Di Como, Charles J., Heitman, Joseph
Rapamycin inhibits the TOR kinases, which regulate cell proliferation and mRNA translation and are conserved from yeast to man. The TOR kinases also regulate responses to nutrients, including...
Litvintseva, Anastasia P., Marra, Robert E., Nielsen, Kirsten, Heitman, Joseph, Vilgalys, Rytas, Mitchell, Thomas G.
The most common cause of fungal meningitis in humans, Cryptococcus neoformans serotype A, is a basidiomycetous yeast with a bipolar mating system. However, the vast majority (>99.9%) of C. neoformans...
Hicks, Julie K., D'Souza, Cletus A., Cox, Gary M., Heitman, Joseph
Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A)....
Apidianakis, Yiorgos, Rahme, Laurence G., Heitman, Joseph, Ausubel, Frederick M., Calderwood, Stephen B., Mylonakis, Eleftherios
We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus...
Cryptococcus neoformans Virulence Gene Discovery through Insertional Mutagenesis
Idnurm, Alexander, Reedy, Jennifer L., Nussbaum, Jesse C., Heitman, Joseph
Insertional mutagenesis was applied to Cryptococcus neoformans to identify genes associated with virulence attributes. Using biolistic transformation, we generated 4,300 nourseothricin...
In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus
Steinbach, William J., Schell, Wiley A., Blankenship, Jill R., Onyewu, Chiatogu, Heitman, Joseph, Perfect, John R.
The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly...
The α-Specific Cell Identity Factor Sxi1α Is Not Required for Virulence of Cryptococcus neoformans
Hull, Christina M., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a human fungal pathogen that has two mating types (a and α). Experiments have shown that in some backgrounds α strains are more virulent than a strains. Our studies...
Nichols, Connie B., Fraser, James A., Heitman, Joseph
Sexual identity and mating are linked to virulence of the fungal pathogen Cryptococcus neoformans. Cells of the α mating type are more prevalent and can be more virulent than a cells, and...
Arévalo-Rodríguez, Miguel, Pan, Xuewen, Boeke, Jef D., Heitman, Joseph
FKBP12 is a conserved member of the prolyl-isomerase enzyme family and serves as the intracellular receptor for FK506 that mediates immunosuppression in mammals and antimicrobial actions in fungi. To...
Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray†
Kraus, Peter R., Boily, Marie-Josée, Giles, Steven S., Stajich, Jason E., Allen, Andria, Cox, Gary M., ...
The ability to survive and proliferate at 37°C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the...
Convergent Evolution of Chromosomal Sex-Determining Regions in the Animal and Fungal Kingdoms
Fraser, James A, Diezmann, Stephanie, Subaran, Ryan L, Allen, Andria, Lengeler, Klaus B, Dietrich, Fred S, ...
Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen...
Onyewu, Chiatogu, Wormley, Floyd L., Perfect, John R., Heitman, Joseph
In Candida albicans, calcineurin is essential for virulence and survival during membrane perturbation by azoles. Crz1 is a proposed downstream target of calcineurin based on studies of Saccharomyces...
Steinbach, William J., Singh, Nina, Miller, Jackie L., Benjamin, Daniel K., Schell, Wiley A., Heitman, Joseph, ...
We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin...
Bahn, Yong-Sun, Hicks, Julie K., Giles, Steven S., Cox, Gary M., Heitman, Joseph
The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human...
Blankenship, Jill R., Singh, Nina, Alexander, Barbara D., Heitman, Joseph
The immunosuppressants tacrolimus (FK506) and cyclosporine A inhibit calcineurin and have potent antifungal activity. In this study, 24% of Cryptococcus neoformans isolates from solid-organ...
Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae†
Arévalo-Rodríguez, Miguel, Heitman, Joseph
Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans...
Pukkila-Worley, Read, Gerrald, Quincy D., Kraus, Peter R., Boily, Marie-Josée, Davis, Matthew J., Giles, Steven S., ...
Cryptococcus neoformans is an opportunistic human fungal pathogen that elaborates several virulence attributes, including a polysaccharide capsule and melanin pigments. A conserved Gα protein/cyclic...
Chromosomal Translocation and Segmental Duplication in Cryptococcus neoformans†
Fraser, James A., Huang, Johnny C., Pukkila-Worley, Read, Alspaugh, J. Andrew, Mitchell, Thomas G., Heitman, Joseph
Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to...
Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom
Idnurm, Alexander, Heitman, Joseph
Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered...
Wang, Ping, Cardenas, Maria E., Cox, Gary M., Perfect, John R., Heitman, Joseph
Cyclophilin A is the target of the immunosuppressant cyclosporin A (CsA) and is encoded by a single unique gene conserved from yeast to humans. In the pathogenic fungus Cryptococcus neoformans, two...
Bahn, Yong-Sun, Kojima, Kaihei, Cox, Gary M., Heitman, Joseph
The human pathogenic fungus Cryptococcus neoformans has diverged from a common ancestor into three biologically distinct varieties or sibling species over the past 10–40 million years. During...
Hull, Christina M., Boily, Marie-Josee, Heitman, Joseph
Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a...
Kraus, Peter R., Nichols, Connie B., Heitman, Joseph
The function of calcium as a signaling molecule is conserved in eukaryotes from fungi to humans. Previous studies have identified the calcium-activated phosphatase calcineurin as a critical factor in...
Cyclophilins belong to a group of proteins known as immunophilins that have peptidyl-prolyl cis-trans somerase activity. Cyclophilins are found in all cells of all organisms studied. Mammalian...
Nielsen, Kirsten, Cox, Gary M., Litvintseva, Anastasia P., Mylonakis, Eleftherios, Malliaris, Stephanie D., Benjamin, Daniel K., ...
Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests...
Fox, Deborah S., Heitman, Joseph
Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated phosphatase that is the target of the...
Clonality and Recombination in Genetically Differentiated Subgroups of Cryptococcus gattii†
Campbell, Leona T., Currie, Bart J., Krockenberger, Mark, Malik, Richard, Meyer, Wieland, Heitman, Joseph, ...
Cryptococcus gattii is a pathogenic yeast that together with Cryptococcus neoformans causes cryptococcosis in humans and animals. High numbers of viable C. gattii propagules can be obtained from...
Campbell, Leona T., Fraser, James A., Nichols, Connie B., Dietrich, Fred S., Carter, Dee, Heitman, Joseph
Cryptococcus gattii is a primary pathogenic yeast that causes disease in both animals and humans. It is closely related to Cryptococcus neoformans and diverged from a common ancestor ∼40 million...
Cryptococcus neoformans Gene Expression during Murine Macrophage Infection†
Fan, Weihua, Kraus, Peter R., Boily, Marie-Josee, Heitman, Joseph
The fungal pathogen Cryptococcus neoformans survives phagocytosis by macrophages and proliferates within, ultimately establishing latent infection as a facultative intracellular pathogen that can...
Calcineurin Is Required for Candida albicans To Survive Calcium Stress in Serum
Blankenship, Jill R., Heitman, Joseph
The calcium-activated protein phosphatase calcineurin plays a critical role in the virulence of Candida albicans. Previous studies demonstrated that calcineurin is not required for the yeast-hypha...
Harashima, Toshiaki, Heitman, Joseph
All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces...
Chlamydospore Formation during Hyphal Growth in Cryptococcus neoformans
Lin, Xiaorong, Heitman, Joseph
Cryptococcus neoformans, a basidiomycetous fungal pathogen, infects hosts through inhalation and can cause fatal meningoencephalitis in individuals if untreated. This fungus undergoes a dimorphic...
Calcineurin: a central controller of signalling in eukaryotes
Aramburu, José, Heitman, Joseph, Crabtree, Gerald R.
Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function
Tang, Robin J., Breger, Julia, Idnurm, Alexander, Gerik, Kimberly J., Lodge, Jennifer K., Heitman, Joseph, ...
Caenorhabditis elegans can serve as a substitute host for the study of microbial pathogenesis. We found that mutations in genes of the fungal pathogen Cryptococcus neoformans involved in mammalian...
Hicks, Julie K., Bahn, Yong-Sun, Heitman, Joseph
The virulence of the human pathogenic fungus Cryptococcus neoformans is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of...
Galleria mellonella as a Model System To Study Cryptococcus neoformans Pathogenesis
Mylonakis, Eleftherios, Moreno, Roberto, El Khoury, Joseph B., Idnurm, Alexander, Heitman, Joseph, Calderwood, Stephen B., ...
Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax...
Reedy, Jennifer L., Husain, Shahid, Ison, Michael, Pruett, Timothy L., Singh, Nina, Heitman, Joseph
In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients...
Bahn, Yong-Sun, Kojima, Kaihei, Cox, Gary M., Heitman, Joseph
The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and...
Nielsen, Kirsten, Marra, Robert E., Hagen, Ferry, Boekhout, Teun, Mitchell, Thomas G., Cox, Gary M., ...
The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects...
Marra, Robert E, Huang, Johnny C, Fung, Eula, Nielsen, Kirsten, Heitman, Joseph, Vilgalys, Rytas, ...
To construct a genetic linkage map of the heterothallic yeast, Cryptococcus neoformans (Filobasidiella neoformans), we crossed two mating-compatible strains and analyzed 94 progeny for the...
Idnurm, Alexander, Rodríguez-Romero, Julio, Corrochano, Luis M., Sanz, Catalina, Iturriaga, Enrique A., Eslava, Arturo P., ...
Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere...
Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus
Steinbach, William J., Cramer, Robert A., Perfect, B. Zachary, Asfaw, Yohannes G., Sauer, Theodor C., Najvar, Laura K., ...
Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of...
Walton, Felicia J., Heitman, Joseph, Idnurm, Alexander
In eukaryotes the complex processes of development, differentiation, and proliferation require carefully orchestrated changes in cellular morphology. Single-celled eukaryotes provide tractable models...
Hsueh, Yen-Ping, Idnurm, Alexander, Heitman, Joseph
Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and,...
Lin, Xiaorong, Huang, Johnny C, Mitchell, Thomas G, Heitman, Joseph
Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and...
Characterization of Alcohol-induced Filamentous Growth in Saccharomyces cerevisiae
Lorenz, Michael C., Cutler, N. Shane, Heitman, Joseph
Diploid cells of the budding yeast Saccharomyces cerevisiae starved for nitrogen differentiate into a filamentous growth form. Poor carbon sources such as starches can also stimulate filamentation,...
Protection from nitrosative stress by yeast flavohemoglobin
Liu, Limin, Zeng, Ming, Hausladen, Alfred, Heitman, Joseph, Stamler, Jonathan S.
Yeast hemoglobin was discovered close to half a century ago, but its function has remained unknown. Herein, we report that this flavohemoglobin protects Saccharomyces cerevisiae from nitrosative...
Lengeler, Klaus B., Wang, Ping, Cox, Gary M., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving mating between haploid MATa and MATα cells. Here we describe the isolation of part of the MATa...
Dolinski, Kara, Muir, Scott, Cardenas, Maria, Heitman, Joseph
The cyclophilins and FK506 binding proteins (FKBPs) bind to cyclosporin A, FK506, and rapamycin and mediate their immunosuppressive and toxic effects, but the physiological functions of these...
Alarcon, Clara M., Heitman, Joseph, Cardenas, Maria E.
In complex with FKBP12, the immunosuppressant rapamycin binds to and inhibits the yeast TOR1 and TOR2 proteins and the mammalian homologue mTOR/FRAP/RAFT1. The TOR proteins promote cell cycle...
Dolinski, Kara, Scholz, Christian, Muir, R. Scott, Rospert, Sabine, Schmid, Franz X., Cardenas, Maria E., ...
Cyclophilin and FK506 binding protein (FKBP) accelerate cis–trans peptidyl-prolyl isomerization and bind to and mediate the effects of the immunosuppressants cyclosporin A and FK506. The normal...
The TOR Signal Transduction Cascade Controls Cellular Differentiation in Response to Nutrients
Cutler, N. Shane, Pan, Xuewen, Heitman, Joseph, Cardenas, Maria E.
Rapamycin binds and inhibits the Tor protein kinases, which function in a nutrient-sensing signal transduction pathway that has been conserved from the yeast Saccharomyces cerevisiae to humans. In...
In response to nitrogen starvation, diploid cells of the yeast Saccharomyces cerevisiae differentiate to a filamentous growth form known as pseudohyphal differentiation. Filamentous growth is...
The G-Protein β Subunit GPB1 Is Required for Mating and Haploid Fruiting in Cryptococcus neoformans
Wang, Ping, Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle. The gene encoding a heterotrimeric G-protein β subunit, GPB1, was cloned and disrupted. gpb1 mutant strains...
D'Souza, Cletus A., Alspaugh, J. Andrew, Yue, Changli, Harashima, Toshiaki, Cox, Gary M., Perfect, John R., ...
Cryptococcus neoformans is an opportunistic fungal pathogen that infects the human central nervous system. This pathogen elaborates two specialized virulence factors: the antioxidant melanin and an...
Cardenas, Maria E., Cruz, M. Cristina, Del Poeta, Maurizio, Chung, Namjin, Perfect, John R., Heitman, Joseph
Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product...
Del Poeta, Maurizio, Chen, Shih-Fong, Von Hoff, Daniel, Dykstra, Christine C., Wani, Mansukh C., Manikumar, Govindarajan, ...
The activities of a series of camptothecin and nitidine derivatives that might interact with topoisomerase I were compared against yeast and cancer cell lines. Our findings reveal that structural...
Cruz, M. Cristina, Del Poeta, Maurizio, Wang, Ping, Wenger, Roland, Zenke, Gerhard, Quesniaux, Valerie F. J., ...
Cyclosporine (CsA) is an immunosuppressive and antimicrobial drug which, in complex with cyclophilin A, inhibits the protein phosphatase calcineurin. We recently found that Cryptococcus neoformans...
Del Poeta, Maurizio, Cruz, M. Cristina, Cardenas, Maria E., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening infections of the central nervous system. Existing therapies include amphotericin B, fluconazole, and...
Cruz, M. Cristina, Goldstein, Alan L., Blankenship, Jill, Del Poeta, Maurizio, Perfect, John R., McCusker, John H., ...
Candida albicans and Cryptococcus neoformans cause both superficial and disseminated infections in humans. Current antifungal therapies for deep-seated infections are limited to amphotericin B,...
Del Poeta, Maurizio, Toffaletti, Dena L., Rude, Thomas H., Sparks, Sara D., Heitman, Joseph, Perfect, John R.
Synthetic green fluorescent protein (GFP) was used as a reporter to detect differential gene expression in the pathogenic fungus Cryptococcus neoformans. Promoters from the C. neoformans actin, GAL7,...
Cruz, M. Cristina, Sia, Rey A. L., Olson, Michael, Cox, Gary M., Heitman, Joseph
The calcineurin gene was cloned and disrupted in serotype D strains of Cryptococcus neoformans. Serotype A and serotype D calcineurin mutants were inviable at 37°C and avirulent in mice, whereas...
Lengeler, Klaus B., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a pathogenic basidiomycete with a defined sexual cycle involving mating between haploid yeast cells with a transient diploid state. C. neoformans occurs in four predominant...
Signal Transduction Cascades Regulating Fungal Development and Virulence
Lengeler, Klaus B., Davidson, Robert C., D'souza, Cletus, Harashima, Toshiaki, Shen, Wei-Chiang, Wang, Ping, ...
Cellular differentiation, mating, and filamentous growth are regulated in many fungi by environmental and nutritional signals. For example, in response to nitrogen limitation, diploid cells of the...
In response to nitrogen limitation, Saccharomyces cerevisiae undergoes a dimorphic transition to filamentous pseudohyphal growth. In previous studies, the transcription factor Sok2 was found to...
Cruz, M. Cristina, Cavallo, Lora M., Görlach, Jenifer M., Cox, Gary, Perfect, John R., Cardenas, Maria E., ...
Cryptococcus neoformans is a fungal pathogen that causes meningitis in patients immunocompromised by AIDS, chemotherapy, organ transplantation, or high-dose steroids. Current antifungal drug...
Zaragoza, Dean, Ghavidel, Ataollah, Heitman, Joseph, Schultz, Michael C.
The macrolide antibiotic rapamycin inhibits cellular proliferation by interfering with the highly conserved TOR (for target of rapamycin) signaling pathway. Growth arrest of budding yeast cells...
Dolinski, Kara J., Cardenas, Maria E., Heitman, Joseph
Cyclophilins are cis-trans-peptidyl-prolyl isomerases that bind to and are inhibited by the immunosuppressant cyclosporin A (CsA). The toxic effects of CsA are mediated by the 18-kDa cyclophilin A...
Shen, Wei-Chiang, Davidson, Robert C., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATα and MATa cells. Interestingly, MATα strains are more common, are more virulent than congenic MATa...
Wang, Ping, Nichols, Connie B., Lengeler, Klaus B., Cardenas, Maria E., Cox, Gary M., Perfect, John R., ...
Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle involving fusion of haploid MATα and MATa cells. Virulence has been linked to the mating type, and MATα cells...
Alspaugh, J. Andrew, Pukkila-Worley, Read, Harashima, Toshiaki, Cavallo, Lora M., Funnell, Deanna, Cox, Gary M., ...
The signaling molecule cyclic AMP (cAMP) is a ubiquitous second messenger that enables cells to detect and respond to extracellular signals. cAMP is generated by the enzyme adenylyl cyclase, which is...
Calcineurin is essential for survival during membrane stress in Candida albicans
Cruz, M.Cristina, Goldstein, Alan L., Blankenship, Jill R., Del Poeta, Maurizio, Davis, Dana, Cardenas, Maria E., ...
The immunosuppressants cyclosporin A (CsA) and FK506 inhibit the protein phosphatase calcineurin and block T-cell activation and transplant rejection. Calcineurin is conserved in microorganisms and...
Mating-Type Locus of Cryptococcus neoformans: a Step in the Evolution of Sex Chromosomes
Lengeler, Klaus B., Fox, Deborah S., Fraser, James A., Allen, Andria, Forrester, Keri, Dietrich, Fred S., ...
The sexual development and virulence of the fungal pathogen Cryptococcus neoformans is controlled by a bipolar mating system determined by a single locus that exists in two alleles, α and a. The α...
Protein Kinase A Operates a Molecular Switch That Governs Yeast Pseudohyphal Differentiation
The yeast Saccharomyces cerevisiae undergoes a dimorphic filamentous transition in response to nutrient cues that is affected by both mitogen-activated protein kinase and cyclic AMP-protein kinase A...
Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis
Mylonakis, Eleftherios, Ausubel, Frederick M., Perfect, John R., Heitman, Joseph, Calderwood, Stephen B.
We found that the well-studied nematode Caenorhabditis elegans can use various yeasts, including Cryptococcus laurentii and Cryptococcus kuetzingii, as a sole source of food, producing similar brood...
Cruz, M.Cristina, Fox, Deborah S., Heitman, Joseph
Cryptococcus neoformans is a fungal pathogen that causes meningitis in immunocompromised patients. Its growth is sensitive to the immunosuppressants FK506 and cyclosporin, which inhibit the Ca2+–...
Onyewu, Chiatogu, Blankenship, Jill R., Del Poeta, Maurizio, Heitman, Joseph
Azoles target the ergosterol biosynthetic enzyme lanosterol 14α-demethylase and are a widely applied class of antifungal agents because of their broad therapeutic window, wide spectrum of activity,...
Roberts, Richard J., Belfort, Marlene, Bestor, Timothy, Bhagwat, Ashok S., Bickle, Thomas A., Bitinaite, Jurate, ...
A nomenclature is described for restriction endonucleases, DNA methyltransferases, homing endonucleases and related genes and gene products. It provides explicit categories for the many different...
Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence
Blankenship, Jill R., Wormley, Floyd L., Boyce, Molly K., Schell, Wiley A., Filler, Scott G., Perfect, John R., ...
Calcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription...
Disruption of Ergosterol Biosynthesis Confers Resistance to Amphotericin B in Candida lusitaniae
Young, Laura Y., Hull, Christina M., Heitman, Joseph
Candida lusitaniae is an emerging human pathogen that, unlike other fungal pathogens, frequently develops resistance to the commonly used antifungal agent amphotericin B. Amphotericin B is a member...
Schein, Jacqueline E., Tangen, Kristin L., Chiu, Readman, Shin, Heesun, Lengeler, Klaus B., MacDonald, William Kim, ...
The basidiomycete fungus Cryptococcus neoformans is an important opportunistic pathogen of humans that poses a significant threat to immunocompromised individuals. Isolates of C. neoformans are...
Sexual Cycle of Cryptococcus neoformans var. grubii and Virulence of Congenic a and α Isolates
Nielsen, Kirsten, Cox, Gary M., Wang, Ping, Toffaletti, Dena L., Perfect, John R., Heitman, Joseph
Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of...
Hull, Christina M., Davidson, Robert C., Heitman, Joseph
Virulence in the human fungal pathogen Cryptococcus neoformans is associated with the α mating type. Studies to identify the properties of α cells that enhance pathogenesis have led to the...
Fox, Deborah S., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients. The Ca2+-calmodulin-activated protein phosphatase...
Fraser, James A., Subaran, Ryan L., Nichols, Connie B., Heitman, Joseph
Cryptococcus neoformans is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens C. neoformans var. neoformans (serotype D) and...
Görlach, Jenifer, Fox, Deborah S., Cutler, N.Shane, Cox, Gary M., Perfect, John R., Heitman, Joseph
Calcineurin is the conserved target of the immunosuppressants cyclosporin A and FK506. Using the yeast two-hybrid system, we identified a novel calcineurin binding protein, CBP1, from the pathogenic...
Wu, Xiaoyun, Wilcox, Cathy B., Devasahayam, Gina, Hackett, Robin L., Arévalo-Rodríguez, Miguel, Cardenas, Maria E., ...
The Ess1/Pin1 peptidyl-prolyl isomerase (PPIase) is thought to control mitosis by binding to cell cycle regulatory proteins and altering their activity. Here we isolate temperature-sensitive ess1...
Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3–Rpd3 histone deacetylase
Arévalo-Rodríguez, Miguel, Cardenas, Maria E., Wu, Xiaoyun, Hanes, Steven D., Heitman, Joseph
Three families of prolyl isomerases have been identified: cyclophilins, FK506-binding proteins (FKBPs) and parvulins. All 12 cyclophilins and FKBPs are dispensable for growth in yeast, whereas the...
Cryptococcus neoformans mating and virulence are regulated by the G-protein α subunit GPA1 and cAMP
Alspaugh, J. Andrew, Perfect, John R., Heitman, Joseph
This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogen Cryptococcus neoformans. The gene encoding a G-protein α...
The TOR signaling cascade regulates gene expression in response to nutrients
Cardenas, Maria E., Cutler, N. Shane, Lorenz, Michael C., Di Como, Charles J., Heitman, Joseph
Rapamycin inhibits the TOR kinases, which regulate cell proliferation and mRNA translation and are conserved from yeast to man. The TOR kinases also regulate responses to nutrients, including...
Litvintseva, Anastasia P., Marra, Robert E., Nielsen, Kirsten, Heitman, Joseph, Vilgalys, Rytas, Mitchell, Thomas G.
The most common cause of fungal meningitis in humans, Cryptococcus neoformans serotype A, is a basidiomycetous yeast with a bipolar mating system. However, the vast majority (>99.9%) of C. neoformans...
Hicks, Julie K., D'Souza, Cletus A., Cox, Gary M., Heitman, Joseph
Our earlier findings established that cyclic AMP-dependent protein kinase functions in a signaling cascade that regulates mating and virulence of Cryptococcus neoformans var. grubii (serotype A)....
Apidianakis, Yiorgos, Rahme, Laurence G., Heitman, Joseph, Ausubel, Frederick M., Calderwood, Stephen B., Mylonakis, Eleftherios
We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus...
Cryptococcus neoformans Virulence Gene Discovery through Insertional Mutagenesis
Idnurm, Alexander, Reedy, Jennifer L., Nussbaum, Jesse C., Heitman, Joseph
Insertional mutagenesis was applied to Cryptococcus neoformans to identify genes associated with virulence attributes. Using biolistic transformation, we generated 4,300 nourseothricin...
In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus
Steinbach, William J., Schell, Wiley A., Blankenship, Jill R., Onyewu, Chiatogu, Heitman, Joseph, Perfect, John R.
The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly...
The α-Specific Cell Identity Factor Sxi1α Is Not Required for Virulence of Cryptococcus neoformans
Hull, Christina M., Cox, Gary M., Heitman, Joseph
Cryptococcus neoformans is a human fungal pathogen that has two mating types (a and α). Experiments have shown that in some backgrounds α strains are more virulent than a strains. Our studies...
Nichols, Connie B., Fraser, James A., Heitman, Joseph
Sexual identity and mating are linked to virulence of the fungal pathogen Cryptococcus neoformans. Cells of the α mating type are more prevalent and can be more virulent than a cells, and...
Arévalo-Rodríguez, Miguel, Pan, Xuewen, Boeke, Jef D., Heitman, Joseph
FKBP12 is a conserved member of the prolyl-isomerase enzyme family and serves as the intracellular receptor for FK506 that mediates immunosuppression in mammals and antimicrobial actions in fungi. To...
Identification of Cryptococcus neoformans Temperature-Regulated Genes with a Genomic-DNA Microarray†
Kraus, Peter R., Boily, Marie-Josée, Giles, Steven S., Stajich, Jason E., Allen, Andria, Cox, Gary M., ...
The ability to survive and proliferate at 37°C is an essential virulence attribute of pathogenic microorganisms. A partial-genome microarray was used to profile gene expression in the...
Convergent Evolution of Chromosomal Sex-Determining Regions in the Animal and Fungal Kingdoms
Fraser, James A, Diezmann, Stephanie, Subaran, Ryan L, Allen, Andria, Lengeler, Klaus B, Dietrich, Fred S, ...
Sexual identity is governed by sex chromosomes in plants and animals, and by mating type (MAT) loci in fungi. Comparative analysis of the MAT locus from a species cluster of the human fungal pathogen...
Onyewu, Chiatogu, Wormley, Floyd L., Perfect, John R., Heitman, Joseph
In Candida albicans, calcineurin is essential for virulence and survival during membrane perturbation by azoles. Crz1 is a proposed downstream target of calcineurin based on studies of Saccharomyces...
Steinbach, William J., Singh, Nina, Miller, Jackie L., Benjamin, Daniel K., Schell, Wiley A., Heitman, Joseph, ...
We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin...
Bahn, Yong-Sun, Hicks, Julie K., Giles, Steven S., Cox, Gary M., Heitman, Joseph
The evolutionarily conserved cyclic AMP (cAMP) signaling pathway controls cell functions in response to environmental cues in organisms as diverse as yeast and mammals. In the basidiomycetous human...
Blankenship, Jill R., Singh, Nina, Alexander, Barbara D., Heitman, Joseph
The immunosuppressants tacrolimus (FK506) and cyclosporine A inhibit calcineurin and have potent antifungal activity. In this study, 24% of Cryptococcus neoformans isolates from solid-organ...
Cyclophilin A Is Localized to the Nucleus and Controls Meiosis in Saccharomyces cerevisiae†
Arévalo-Rodríguez, Miguel, Heitman, Joseph
Cyclophilin A is conserved from yeast to humans and mediates the ability of cyclosporine to perturb signal transduction cascades via inhibition of calcineurin. Cyclophilin A also catalyzes cis-trans...
Pukkila-Worley, Read, Gerrald, Quincy D., Kraus, Peter R., Boily, Marie-Josée, Davis, Matthew J., Giles, Steven S., ...
Cryptococcus neoformans is an opportunistic human fungal pathogen that elaborates several virulence attributes, including a polysaccharide capsule and melanin pigments. A conserved Gα protein/cyclic...
Chromosomal Translocation and Segmental Duplication in Cryptococcus neoformans†
Fraser, James A., Huang, Johnny C., Pukkila-Worley, Read, Alspaugh, J. Andrew, Mitchell, Thomas G., Heitman, Joseph
Large chromosomal events such as translocations and segmental duplications enable rapid adaptation to new environments. Here we marshal genomic, genetic, meiotic mapping, and physical evidence to...
Light Controls Growth and Development via a Conserved Pathway in the Fungal Kingdom
Idnurm, Alexander, Heitman, Joseph
Light inhibits mating and haploid fruiting of the human fungal pathogen Cryptococcus neoformans, but the mechanisms involved were unknown. Two genes controlling light responses were discovered...
Wang, Ping, Cardenas, Maria E., Cox, Gary M., Perfect, John R., Heitman, Joseph
Cyclophilin A is the target of the immunosuppressant cyclosporin A (CsA) and is encoded by a single unique gene conserved from yeast to humans. In the pathogenic fungus Cryptococcus neoformans, two...
Bahn, Yong-Sun, Kojima, Kaihei, Cox, Gary M., Heitman, Joseph
The human pathogenic fungus Cryptococcus neoformans has diverged from a common ancestor into three biologically distinct varieties or sibling species over the past 10–40 million years. During...
Hull, Christina M., Boily, Marie-Josee, Heitman, Joseph
Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a...
Kraus, Peter R., Nichols, Connie B., Heitman, Joseph
The function of calcium as a signaling molecule is conserved in eukaryotes from fungi to humans. Previous studies have identified the calcium-activated phosphatase calcineurin as a critical factor in...
Galleria mellonella as a Model System To Study Cryptococcus neoformans Pathogenesis
Mylonakis, Eleftherios, Moreno, Roberto, El Khoury, Joseph B., Idnurm, Alexander, Heitman, Joseph, Calderwood, Stephen B., ...
Evaluation of Cryptococcus neoformans virulence in a number of nonmammalian hosts suggests that C. neoformans is a nonspecific pathogen. We used the killing of Galleria mellonella (the greater wax...
Cyclophilins belong to a group of proteins known as immunophilins that have peptidyl-prolyl cis-trans somerase activity. Cyclophilins are found in all cells of all organisms studied. Mammalian...
Nielsen, Kirsten, Cox, Gary M., Litvintseva, Anastasia P., Mylonakis, Eleftherios, Malliaris, Stephanie D., Benjamin, Daniel K., ...
Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests...
Fox, Deborah S., Heitman, Joseph
Mating and virulence of the human fungal pathogen Cryptococcus neoformans are controlled by calcineurin, a serine-threonine-specific calcium-activated phosphatase that is the target of the...
Clonality and Recombination in Genetically Differentiated Subgroups of Cryptococcus gattii†
Campbell, Leona T., Currie, Bart J., Krockenberger, Mark, Malik, Richard, Meyer, Wieland, Heitman, Joseph, ...
Cryptococcus gattii is a pathogenic yeast that together with Cryptococcus neoformans causes cryptococcosis in humans and animals. High numbers of viable C. gattii propagules can be obtained from...
Campbell, Leona T., Fraser, James A., Nichols, Connie B., Dietrich, Fred S., Carter, Dee, Heitman, Joseph
Cryptococcus gattii is a primary pathogenic yeast that causes disease in both animals and humans. It is closely related to Cryptococcus neoformans and diverged from a common ancestor ∼40 million...
Cryptococcus neoformans Gene Expression during Murine Macrophage Infection†
Fan, Weihua, Kraus, Peter R., Boily, Marie-Josee, Heitman, Joseph
The fungal pathogen Cryptococcus neoformans survives phagocytosis by macrophages and proliferates within, ultimately establishing latent infection as a facultative intracellular pathogen that can...
Calcineurin Is Required for Candida albicans To Survive Calcium Stress in Serum
Blankenship, Jill R., Heitman, Joseph
The calcium-activated protein phosphatase calcineurin plays a critical role in the virulence of Candida albicans. Previous studies demonstrated that calcineurin is not required for the yeast-hypha...
Harashima, Toshiaki, Heitman, Joseph
All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces...
Chlamydospore Formation during Hyphal Growth in Cryptococcus neoformans
Lin, Xiaorong, Heitman, Joseph
Cryptococcus neoformans, a basidiomycetous fungal pathogen, infects hosts through inhalation and can cause fatal meningoencephalitis in individuals if untreated. This fungus undergoes a dimorphic...
Calcineurin: a central controller of signalling in eukaryotes
Aramburu, José, Heitman, Joseph, Crabtree, Gerald R.
Workshop on the Calcium/Calcineurin/NFAT Pathway: Regulation and Function
Tang, Robin J., Breger, Julia, Idnurm, Alexander, Gerik, Kimberly J., Lodge, Jennifer K., Heitman, Joseph, ...
Caenorhabditis elegans can serve as a substitute host for the study of microbial pathogenesis. We found that mutations in genes of the fungal pathogen Cryptococcus neoformans involved in mammalian...
Hicks, Julie K., Bahn, Yong-Sun, Heitman, Joseph
The virulence of the human pathogenic fungus Cryptococcus neoformans is regulated by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) signaling cascade that promotes mating and the production of...
Xue, Chaoyang, Bahn, Yong-Sun, Cox, Gary M., Heitman, Joseph
The Gα protein Gpa1 governs the cAMP-PKA signaling pathway and plays a central role in virulence and differentiation in the human fungal pathogen Cryptococcus neoformans, but the signals and...
Reedy, Jennifer L., Husain, Shahid, Ison, Michael, Pruett, Timothy L., Singh, Nina, Heitman, Joseph
In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients...
Idnurm, Alexander, Rodríguez-Romero, Julio, Corrochano, Luis M., Sanz, Catalina, Iturriaga, Enrique A., Eslava, Arturo P., ...
Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere...
Nielsen, Kirsten, Marra, Robert E., Hagen, Ferry, Boekhout, Teun, Mitchell, Thomas G., Cox, Gary M., ...
The study of quantitative traits provides a window on the interactions between multiple unlinked genetic loci. The interaction between hosts and pathogenic microbes, such as fungi, involves aspects...
Marra, Robert E, Huang, Johnny C, Fung, Eula, Nielsen, Kirsten, Heitman, Joseph, Vilgalys, Rytas, ...
To construct a genetic linkage map of the heterothallic yeast, Cryptococcus neoformans (Filobasidiella neoformans), we crossed two mating-compatible strains and analyzed 94 progeny for the...
Bahn, Yong-Sun, Kojima, Kaihei, Cox, Gary M., Heitman, Joseph
The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and...
Calcineurin Controls Growth, Morphology, and Pathogenicity in Aspergillus fumigatus
Steinbach, William J., Cramer, Robert A., Perfect, B. Zachary, Asfaw, Yohannes G., Sauer, Theodor C., Najvar, Laura K., ...
Calcineurin is implicated in a myriad of human diseases as well as homeostasis and virulence in several major human pathogenic microorganisms. The fungus Aspergillus fumigatus is a leading cause of...
Walton, Felicia J., Heitman, Joseph, Idnurm, Alexander
In eukaryotes the complex processes of development, differentiation, and proliferation require carefully orchestrated changes in cellular morphology. Single-celled eukaryotes provide tractable models...
Hsueh, Yen-Ping, Idnurm, Alexander, Heitman, Joseph
Recombination increases dramatically during meiosis to promote genetic exchange and generate recombinant progeny. Interestingly, meiotic recombination is unevenly distributed throughout genomes, and,...
Lin, Xiaorong, Huang, Johnny C, Mitchell, Thomas G, Heitman, Joseph
Cryptococcus neoformans is a fungal human pathogen with a bipolar mating system. It undergoes a dimorphic transition from a unicellular yeast to hyphal filamentous growth during mating and...
Onyewu, Chiatogu, Afshari, Natalie A., Heitman, Joseph
In an established Candida albicans murine keratitis model, combination therapy with ophthalmic preparations of fluconazole and cyclosporine A (CsA) demonstrated in vivo drug synergy and effectively...
Peroxisome Function Regulates Growth on Glucose in the Basidiomycete Fungus Cryptococcus neoformans▿
Idnurm, Alexander, Giles, Steven S., Perfect, John R., Heitman, Joseph
The function of the peroxisomes was examined in the pathogenic basidiomycete Cryptococcus neoformans. Recent studies reveal the glyoxylate pathway is required for virulence of diverse microbial...
Hicks, Julie K., Heitman, Joseph
Gene duplication and divergence via both the loss and gain of gene activities are powerful evolutionary forces underlying the origin of new biological functions. Here a comparative genetics approach...
Fraser, James A., Stajich, Jason E., Tarcha, Eric J., Cole, Garry T., Inglis, Diane O., Sil, Anita, ...
Sexual reproduction of fungi is governed by the mating type (MAT) locus, a specialized region of the genome encoding key transcriptional regulators that direct regulatory networks to specify cell...
Many Globally Isolated AD Hybrid Strains of Cryptococcus neoformans Originated in Africa
Litvintseva, Anastasia P, Lin, Xiaorong, Templeton, Irka, Heitman, Joseph, Mitchell, Thomas G
Interspecific and intervarietal hybridization may contribute to the biological diversity of fungal populations. Cryptococcus neoformans is a pathogenic yeast and the most common fungal cause of...
Nielsen, Kirsten, De Obaldia, Anna L., Heitman, Joseph
The ecological niche that a species can occupy is determined by its resource requirements and the physical conditions necessary for survival. The niche to which an organism is most highly adapted is...
Hsueh, Yen-Ping, Xue, Chaoyang, Heitman, Joseph
Communication between cells and their environments is often mediated by G protein-coupled receptors and cognate G proteins. In fungi, one such signaling cascade is the mating pathway triggered by...
αADα Hybrids of Cryptococcus neoformans: Evidence of Same-Sex Mating in Nature and Hybrid Fitness
Lin, Xiaorong, Litvintseva, Anastasia P, Nielsen, Kirsten, Patel, Sweta, Floyd, Anna, Mitchell, Thomas G, ...
Cryptococcus neoformans is a ubiquitous human fungal pathogen that causes meningoencephalitis in predominantly immunocompromised hosts. The fungus is typically haploid, and sexual reproduction...
Fan, Weihua, Idnurm, Alexander, Breger, Julia, Mylonakis, Eleftherios, Heitman, Joseph
The basidiomycetous fungal pathogen Cryptococcus neoformans is adapted to survive challenges in the soil and environment and within the unique setting of the mammalian host. A C. neoformans mutant...
Calcineurin Inhibition or Mutation Enhances Cell Wall Inhibitors against Aspergillus fumigatus▿
Steinbach, William J., Cramer, Robert A., Perfect, B. Zachary, Henn, Christina, Nielsen, Kirsten, Heitman, Joseph, ...
Calcineurin mutation or inhibition enhanced the antifungal morphological effect of cell wall inhibitors caspofungin or nikkomycin Z against Aspergillus fumigatus. Quantification of 1,3-β-d-glucan...
Onyewu, Chiatogu, Eads, Emily, Schell, Wiley A., Perfect, John R., Ullmann, Yehuda, Kaufman, Gil, ...
Fluconazole-FK506 or fluconazole-cyclosporine drug combinations were tested in an ex vivo Trichophyton mentagrophytes human skin infection model. Conidia colonization was monitored by scanning...
Upton, Arlo, Fraser, James A., Kidd, Sarah E., Bretz, Camille, Bartlett, Karen H., Heitman, Joseph, ...
We report a case of cryptococcosis due to C. gattii which appears to have been acquired in the Puget Sound region, Washington State. Genotyping confirmed identity to the predominant Vancouver Island...
Bahn, Yong-Sun, Geunes-Boyer, Scarlett, Heitman, Joseph
The stress-activated p38/Hog1 mitogen-activated protein kinase (MAPK) pathway is structurally conserved in many diverse organisms, including fungi and mammals, and modulates myriad cellular...
Kontoyiannis, Dimitrios P., Lewis, Russell E., Alexander, Barbara D., Lortholary, Olivier, Dromer, Françoise, Gupta, Krishan L., ...
Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may...
Teichert, Sabine, Rutherford, Julian C., Wottawa, Marieke, Heitman, Joseph, Tudzynski, Bettina
In Fusarium fujikuroi, the production of gibberellins and bikaverin is repressed by nitrogen sources such as glutamine or ammonium. Sensing and uptake of ammonium by specific permeases play key roles...
Rutherford, Julian C., Lin, Xiaorong, Nielsen, Kirsten, Heitman, Joseph
The conserved AmtB/Mep/Rh family of proteins mediate the transport of ammonium across cellular membranes in a wide range of organisms. Certain fungal members of this group are required to initiate...
Synergistic Effect of Calcineurin Inhibitors and Fluconazole against Candida albicans Biofilms▿
Uppuluri, Priya, Nett, Jeniel, Heitman, Joseph, Andes, David
Calcineurin is a Ca2+-calmodulin-activated serine/threonine-specific protein phosphatase that governs multiple aspects of fungal physiology, including cation homeostasis, morphogenesis, antifungal...
Rutherford, Julian C., Chua, Gordon, Hughes, Timothy, Cardenas, Maria E., Heitman, Joseph
The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a...
Cramer, Robert A., Perfect, B. Zachary, Pinchai, Nadthanan, Park, Steven, Perlin, David S., Asfaw, Yohannes G., ...
The calcineurin pathway is a critical signal transduction pathway in fungi that mediates growth, morphology, stress responses, and pathogenicity. The importance of the calcineurin pathway in fungal...
Impact of Mating Type, Serotype, and Ploidy on the Virulence of Cryptococcus neoformans▿ †
Lin, Xiaorong, Nielsen, Kirsten, Patel, Sweta, Heitman, Joseph
Hybridization with polyploidization is a significant biological force driving evolution. The effect of combining two distinct genomes in one organism on the virulence potential of pathogenic fungi is...
Lin, Xiaorong, Patel, Sweta, Litvintseva, Anastasia P., Floyd, Anna, Mitchell, Thomas G., Heitman, Joseph
The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly...
The Protein Kinase Tor1 Regulates Adhesin Gene Expression in Candida albicans
Bastidas, Robert J., Heitman, Joseph, Cardenas, Maria E.
Eukaryotic cell growth is coordinated in response to nutrient availability, growth factors, and environmental stimuli, enabling cell–cell interactions that promote survival. The rapamycin-sensitive...
Juvvadi, Praveen Rao, Fortwendel, Jarrod R., Pinchai, Nadthanan, Perfect, B. Zachary, Heitman, Joseph, Steinbach, William J.
A functional calcineurin A fusion to enhanced green fluorescent protein (EGFP), CnaA-EGFP, was expressed in the Aspergillus fumigatus ΔcnaA mutant. CnaA-EGFP localized in actively growing hyphal...
Hsueh, Yen-Ping, Fraser, James A., Heitman, Joseph
Sex is orchestrated by the mating-type locus (MAT) in fungi and by sex chromosomes in plants and animals. In fungi, two patterns of sexuality occur: bipolar with a single, typically biallelic sex...
Bui, Tien, Lin, Xiaorong, Malik, Richard, Heitman, Joseph, Carter, Dee
Sexual reproduction and genetic exchange are important for the evolution of fungal pathogens and for producing potentially infective spores. Studies to determine whether sex occurs in the pathogenic...
Byrnes, Edmond J., Li, Wenjun, Lewit, Yonathan, Perfect, John R., Carter, Dee A., Cox, Gary M., ...
In 2007, the first confirmed case of Cryptococcus gattii was reported in the state of North Carolina, USA. An otherwise healthy HIV negative male patient presented with a large upper thigh...
Jain, Neena, Li, Li, Hsueh, Ye-Ping, Guerrero, Abraham, Heitman, Joseph, Goldman, David L., ...
Microbial survival in a host is usually dependent on the ability of a pathogen to undergo changes that promote escape from host defense mechanisms. The human-pathogenic fungus Cryptococcus neoformans...
Findley, Keisha, Rodriguez-Carres, Marianela, Metin, Banu, Kroiss, Johannes, Fonseca, Álvaro, Vilgalys, Rytas, ...
The basidiomycetous yeasts Cryptococcus neoformans and Cryptococcus gattii are closely related sibling species that cause respiratory and neurological disease in humans and animals. Within these two...
Idnurm, Alexander, Walton, Felicia J., Floyd, Anna, Reedy, Jennifer L., Heitman, Joseph
A library of more than 4,500 signature-tagged insertion mutants of the human pathogenic fungus Cryptococcus neoformans was generated, and a subset was screened in a murine inhalation model to...
Aspergillus fumigatus Calcipressin CbpA Is Involved in Hyphal Growth and Calcium Homeostasis▿ †
Pinchai, Nadthanan, Perfect, B. Zachary, Juvvadi, Praveen Rao, Fortwendel, Jarrod R., Cramer, Robert A., Asfaw, Yohannes G., ...
Calcineurin is a conserved protein phosphatase that plays a critical role in Ca2+ signaling and stress responses. Previously, a new class of conserved calcineurin-binding proteins, the calcipressins,...
Sanz, Catalina, Rodríguez-Romero, Julio, Idnurm, Alexander, Christie, John M., Heitman, Joseph, Corrochano, Luis M., ...
The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting...
Lee, Soo Chan, Weiss, Louis M, Heitman, Joseph
Microsporidia are obligate intracellular pathogens mainly infecting both vertebrate and invertebrate hosts. The group comprises approximately 150 genera with 1,200 species. Due to sequence divergence...