William R. Bishai

Altered cellular infiltration and cytokine levels during early Mycobacterium tuberculosissigCmutant infection are associated with late-stage disease attenuation and milder immunopathology in mice (2008)

Abdul-Majid, Khairul-Bariah, Ly, Lan H, Converse, Paul J, Geiman, Deborah E, McMurray, David N, Bishai, William R

Abstract Background Mouse virulence assessments of certain Mycobacterium tuberculosis mutants have revealed an immunopathology defect in which high tissue CFU counts are observed but the tissue...

Daily Dosing of Rifapentine Cures Tuberculosis in Three Months or Less in the Murine Model (2007)

Ian M. Rosenthal, Ming Zhang, Kathy N. Williams, Charles A. Peloquin, Sandeep Tyagi, Andrew A. Vernon, ...

BackgroundAvailability of an ultra-short-course drug regimen capable of curing patients with tuberculosis in 2 to 3 mo would significantly improve global control efforts. Because immediate prospects...

Method to integrate multiple plasmids into the mycobacterial chromosome (2004)

Saviola, Beatrice, Bishai, William R.

In order to create a system in which two independent plasmids can be integrated into a mycobacterial chromosome, a mycobacterial plasmid was constructed containing the phage attachment site attP from...

Construction and characterization of a Mycobacterium tuberculosis mutant lacking the alternate sigma factor gene, sigF. (2000)

Chen, Ping, Ruiz, Rafael E., Li, Qing, Silver, Richard F., Bishai, William R., Kaufmann, S. H. E.

The alternate RNA polymerase sigma factor gene, sigF, which is expressed in stationary phase and under stress conditions in vitro, has been deleted in the virulent CDC1551 strain of Mycobacterium...

Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis (1999)

Parrish, Nikki M., Kuhajda, Francis P., Heine, Henry S., Bishai, William R., Dick, James D.

Cerulenin is a potent inhibitor of fatty acid synthase (FAS) in a variety of prokaryotic and eukaryotic cells. Using a standardized mycobacterial susceptibility test, we have observed that cerulenin...

Regulation of the Escherichia coli water channel gene aqpZ

Calamita, Giuseppe, Kempf, Bettina, Bonhivers, Mélanie, Bishai, William R., Bremer, Erhard, Agre, Peter

Osmotic movement of water across bacterial cell membranes is postulated to be a homeostatic mechanism for maintaining cell turgor. The molecular water transporter remained elusive until discovery of...

Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor

Manabe, Yukari C., Saviola, Beatrice J., Sun, Li, Murphy, John R., Bishai, William R.

Iron is an essential nutrient for the survival of most organisms and has played a central role in the virulence of many infectious disease pathogens. Mycobacterial IdeR is an iron-dependent repressor...

whmD is an essential mycobacterial gene required for proper septation and cell division

Gomez, James E., Bishai, William R.

A study of potential mycobacterial regulatory genes led to the isolation of the Mycobacterium smegmatis whmD gene, which encodes a homologue of WhiB, a Streptomyces coelicolor protein required for...

Epidemiologic Usefulness of Spoligotyping for Secondary Typing of Mycobacterium tuberculosis Isolates with Low Copy Numbers of IS6110

Cronin, Wendy A., Golub, Jonathan E., Magder, Laurence S., Baruch, Nancy G., Lathan, Monica J., Mukasa, Leonard N., ...

Restriction fragment length polymorphism (RFLP) analysis of IS6110 is commonly used to DNA fingerprint Mycobacterium tuberculosis. However, low-copy (≤5) IS6110 M. tuberculosis strains are poorly...

Moxifloxacin (BAY12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis

Miyazaki, Eishi, Miyazaki, Miki, Chen, Jong Min, Chaisson, Richard E., Bishai, William R.

Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro. We tested moxifloxacin for activity in mice against M. tuberculosis CSU93, a...

Exposure to Antibiotics Induces Expression of the Mycobacterium tuberculosis sigF Gene: Implications for Chemotherapy against Mycobacterial Persistors

Michele, Theresa M., Ko, Chiew, Bishai, William R.

The sigF gene encodes an alternate sigma factor found in Mycobacterium tuberculosis and related pathogenic mycobacteria. Determination of conditions of sigF expression is an important step in...

Analysis of Rifapentine for Preventive Therapy in the Cornell Mouse Model of Latent Tuberculosis

Miyazaki, Eishi, Chaisson, Richard E., Bishai, William R.

Rifapentine is a long-acting rifamycin which may be useful for intermittent drug therapy against tuberculosis. In this study we measured the efficacies of rifapentine-containing intermittent drug...

The Staphylococcus aureus rsbW (orf159) Gene Encodes an Anti-Sigma Factor of SigB

Miyazaki, Eishi, Chen, Jong-Min, Ko, Chiew, Bishai, William R.

SigB, a newly discovered alternative sigma factor of Staphylococcus aureus, has been shown to play an important role in stress responses and the regulation of virulence factors. The rsbW (orf159)...

Conditional Sigma Factor Expression, Using the Inducible Acetamidase Promoter, Reveals that the Mycobacterium tuberculosis sigF Gene Modulates Expression of the 16-Kilodalton Alpha-Crystallin Homologue

Manabe, Yukari C., Chen, Jong Min, Ko, Chiew G., Chen, Ping, Bishai, William R.

A chemically inducible acetamidase promoter-sigF fusion gene was integrated into the chromosome of Mycobacterium bovis BCG. Two-dimensional protein gel analysis permitted the identification of a...

Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in Rabbits Evaluated by Lurie’s Pulmonary Tubercle Count Method

Bishai, William R., Dannenberg, Arthur M., Parrish, Nikki, Ruiz, Rafael, Chen, Ping, Zook, Bernard C., ...

The virulence of the CDC1551 strain of Mycobacterium tuberculosis was compared to that of H37Rv in a rabbit inhalation model. While rabbits that inhaled the two strains produced equal numbers of...

Construction and Characterization of a Mycobacterium tuberculosis Mutant Lacking the Alternate Sigma Factor Gene, sigF

Chen, Ping, Ruiz, Rafael E., Li, Qing, Silver, Richard F., Bishai, William R.

The alternate RNA polymerase sigma factor gene, sigF, which is expressed in stationary phase and under stress conditions in vitro, has been deleted in the virulent CDC1551 strain of Mycobacterium...

Novel Selection for Isoniazid (INH) Resistance Genes Supports a Role for NAD+-Binding Proteins in Mycobacterial INH Resistance

Chen, Ping, Bishai, William R.

The genetic basis of isoniazid (INH) resistance remains unknown for a significant proportion of clinical isolates. To identify genes which might confer resistance by detoxifying or sequestering INH,...

Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative σ factor, SigH

Kaushal, Deepak, Schroeder, Benjamin G., Tyagi, Sandeep, Yoshimatsu, Tetsuyuki, Scott, Cherise, Ko, Chiew, ...

The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series of adaptive bacterial virulence factors and inappropriate host immune responses...

Naturally Attenuated, Orally Administered Mycobacterium microti as a Tuberculosis Vaccine Is Better than Subcutaneous Mycobacterium bovis BCG

Manabe, Yukari C., Scott, Cherise P., Bishai, William R.

Mycobacterium microti is phylogenetically closely related to Mycobacterium tuberculosis and is a member of that complex of organisms. It is a curved, acid-fast bacillus that is naturally attenuated...

Comparison of C18-Carboxypropylbetaine and Standard N-Acetyl-l-Cysteine-NaOH Processing of Respiratory Specimens for Increasing Tuberculosis Smear Sensitivity in Brazil

Scott, Cherise P., Dos Anjos Filho, Luciano, De Queiroz Mello, Fernanda Carvalho, Thornton, Charles G., Bishai, William R., Fonseca, Leila S., ...

Techniques to improve the sensitivity of smear microscopy would facilitate early tuberculosis (TB) diagnosis and disease control, especially in low-income countries where the positive predictive...

Field Evaluation of a Rapid Immunochromatographic Test for Tuberculosis

Gounder, Celine, De Queiroz Mello, Fernanda Carvalho, Conde, Marcus B., Bishai, William R., Kritski, Afrânio L., Chaisson, Richard E., ...

Rapid diagnostic tests for tuberculosis (TB) are needed to facilitate early treatment of TB and prevention of Mycobacterium tuberculosis transmission. The ICT Tuberculosis test is a rapid, card-based...

Isolation of Acid-Inducible Genes of Mycobacterium tuberculosis with the Use of Recombinase-Based In Vivo Expression Technology

Saviola, Beatrice, Woolwine, Samuel C., Bishai, William R.

A better understanding of mycobacterial gene regulation under certain stress conditions (e.g., low pH) may provide insight into mechanisms of adaptation during infection. To identify mycobacterial...

Characterization of the Role of the Divalent Metal Ion-Dependent Transcriptional Repressor MntR in the Virulence of Staphylococcus aureus

Ando, Masaru, Manabe, Yukari C., Converse, Paul J., Miyazaki, Eishi, Harrison, Robert, Murphy, John R., ...

DtxR-type metal ion-dependent repressors, present in many bacterial pathogens, may regulate expression of virulence genes such as that encoding diphtheria toxin. SirR, a DtxR homologue initially...

Performance of the Microscopic Observation Drug Susceptibility Assay in Drug Susceptibility Testing for Mycobacterium tuberculosis

Park, Walter G., Bishai, William R., Chaisson, Richard E., Dorman, Susan E.

The drug susceptibility testing performance of a broth-based method with microscopic reading of bacillary growth, the microscopic observation drug susceptibility (MODS) assay, was compared to that of...

A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: Application to Mycobacterium tuberculosis

Lamichhane, Gyanu, Zignol, Matteo, Blades, Natalie J., Geiman, Deborah E., Dougherty, Annette, Grosset, Jacques, ...

We describe a postgenomic in silico approach for identifying genes that are likely to be essential and estimate their proportion in haploid genomes. With the knowledge of all sites eligible for...

Different Strains of Mycobacterium tuberculosis Cause Various Spectrums of Disease in the Rabbit Model of Tuberculosis

Manabe, Yukari C., Dannenberg, Arthur M., Tyagi, Sandeep K., Hatem, Christine L., Yoder, Mark, Woolwine, Samuel C., ...

The rabbit model of tuberculosis has been used historically to differentiate between Mycobacterium tuberculosis and Mycobacterium bovis based on their relative virulence in this animal host. M....

Deletion of Mycobacterium tuberculosis Sigma Factor E Results in Delayed Time to Death with Bacterial Persistence in the Lungs of Aerosol-Infected Mice

Ando, Masaru, Yoshimatsu, Tetsuyuki, Ko, Chiew, Converse, Paul J., Bishai, William R.

The stress-induced extracytoplasmic sigma factor E (SigE) of Mycobacterium tuberculosis shows increased expression after heat shock, sodium dodecyl sulfate treatment, and oxidative stress, as well as...

Susceptibility to Tuberculosis: Clues from Studies with Inbred and Outbred New Zealand White Rabbits

Dorman, Susan E., Hatem, Christine L., Tyagi, Sandeep, Aird, Katherine, Lopez-Molina, Javier, Pitt, M. Louise M., ...

The rabbit model of tuberculosis (TB) is important because rabbits develop a disease that is similar to TB in humans, namely, granulomas with caseous necrosis, liquefaction, and cavities. We describe...

Attenuation of Late-Stage Disease in Mice Infected by the Mycobacterium tuberculosis Mutant Lacking the SigF Alternate Sigma Factor and Identification of SigF-Dependent Genes by Microarray Analysis

Geiman, Deborah E., Kaushal, Deepak, Ko, Chiew, Tyagi, Sandeep, Manabe, Yukari C., Schroeder, Benjamin G., ...

The Mycobacterium tuberculosis alternate sigma factor, SigF, is expressed during stationary growth phase and under stress conditions in vitro. To better understand the function of SigF we studied the...

Method to integrate multiple plasmids into the mycobacterial chromosome

Saviola, Beatrice, Bishai, William R.

In order to create a system in which two independent plasmids can be integrated into a mycobacterial chromosome, a mycobacterial plasmid was constructed containing the phage attachment site attP from...

Modeling In Vivo Pharmacokinetics and Pharmacodynamics of Moxifloxacin Therapy for Mycobacterium tuberculosis Infection by Using a Novel Cartridge System

Ginsburg, Amy Sarah, Lee, Jin, Woolwine, Samuel C., Grosset, Jacques H., Hamzeh, Fayez M., Bishai, William R.

To study the efficacy of moxifloxacin treatment for tuberculosis, we utilized a novel cartridge system to simulate in vivo pharmacokinetics. We found this system to be a robust method for modeling in...

Designer Arrays for Defined Mutant Analysis To Detect Genes Essential for Survival of Mycobacterium tuberculosis in Mouse Lungs

Lamichhane, Gyanu, Tyagi, Sandeep, Bishai, William R.

The mechanisms by which Mycobacterium tuberculosis elicits disease are complex, involving a large repertoire of bacterial genes that are required for in vivo growth and survival. To identify such...

Emergence of Fluoroquinolone Resistance in Mycobacterium tuberculosis during Continuously Dosed Moxifloxacin Monotherapy in a Mouse Model

Ginsburg, Amy Sarah, Sun, Ronggai, Calamita, Heather, Scott, Cherise P., Bishai, William R., Grosset, Jacques H.

Fluoroquinolone resistance in tuberculosis may rapidly emerge. Mice infected with high titers of aerosolized Mycobacterium tuberculosis and treated for 8 weeks with four concentrations of...

Differential Gene Expression in Response to Exposure to Antimycobacterial Agents and Other Stress Conditions among Seven Mycobacterium tuberculosis whiB-Like Genes

Geiman, Deborah E., Raghunand, Tirumalai R., Agarwal, Nisheeth, Bishai, William R.

The seven Mycobacterium tuberculosis whiB-like genes encode small proteins postulated to be transcriptional regulators. A systematic real-time reverse transcription-PCR analysis following exposure to...

Combination Chemotherapy with the Nitroimidazopyran PA-824 and First-Line Drugs in a Murine Model of Tuberculosis†

Nuermberger, Eric, Rosenthal, Ian, Tyagi, Sandeep, Williams, Kathy N., Almeida, Deepak, Peloquin, Charles A., ...

The creation of new chemotherapeutic regimens that permit shortening the duration of treatment is a major priority for antituberculosis drug development. In this study, we used the murine model of...

Regulation of the Escherichia coli water channel gene aqpZ

Calamita, Giuseppe, Kempf, Bettina, Bonhivers, Mélanie, Bishai, William R., Bremer, Erhard, Agre, Peter

Osmotic movement of water across bacterial cell membranes is postulated to be a homeostatic mechanism for maintaining cell turgor. The molecular water transporter remained elusive until discovery of...

Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor

Manabe, Yukari C., Saviola, Beatrice J., Sun, Li, Murphy, John R., Bishai, William R.

Iron is an essential nutrient for the survival of most organisms and has played a central role in the virulence of many infectious disease pathogens. Mycobacterial IdeR is an iron-dependent repressor...

whmD is an essential mycobacterial gene required for proper septation and cell division

Gomez, James E., Bishai, William R.

A study of potential mycobacterial regulatory genes led to the isolation of the Mycobacterium smegmatis whmD gene, which encodes a homologue of WhiB, a Streptomyces coelicolor protein required for...

Epidemiologic Usefulness of Spoligotyping for Secondary Typing of Mycobacterium tuberculosis Isolates with Low Copy Numbers of IS6110

Cronin, Wendy A., Golub, Jonathan E., Magder, Laurence S., Baruch, Nancy G., Lathan, Monica J., Mukasa, Leonard N., ...

Restriction fragment length polymorphism (RFLP) analysis of IS6110 is commonly used to DNA fingerprint Mycobacterium tuberculosis. However, low-copy (≤5) IS6110 M. tuberculosis strains are poorly...

Moxifloxacin (BAY12-8039), a New 8-Methoxyquinolone, Is Active in a Mouse Model of Tuberculosis

Miyazaki, Eishi, Miyazaki, Miki, Chen, Jong Min, Chaisson, Richard E., Bishai, William R.

Moxifloxacin (BAY12-8039) is a new 8-methoxyquinolone shown to be active against Mycobacterium tuberculosis in vitro. We tested moxifloxacin for activity in mice against M. tuberculosis CSU93, a...

Exposure to Antibiotics Induces Expression of the Mycobacterium tuberculosis sigF Gene: Implications for Chemotherapy against Mycobacterial Persistors

Michele, Theresa M., Ko, Chiew, Bishai, William R.

The sigF gene encodes an alternate sigma factor found in Mycobacterium tuberculosis and related pathogenic mycobacteria. Determination of conditions of sigF expression is an important step in...

Analysis of Rifapentine for Preventive Therapy in the Cornell Mouse Model of Latent Tuberculosis

Miyazaki, Eishi, Chaisson, Richard E., Bishai, William R.

Rifapentine is a long-acting rifamycin which may be useful for intermittent drug therapy against tuberculosis. In this study we measured the efficacies of rifapentine-containing intermittent drug...

The Staphylococcus aureus rsbW (orf159) Gene Encodes an Anti-Sigma Factor of SigB

Miyazaki, Eishi, Chen, Jong-Min, Ko, Chiew, Bishai, William R.

SigB, a newly discovered alternative sigma factor of Staphylococcus aureus, has been shown to play an important role in stress responses and the regulation of virulence factors. The rsbW (orf159)...

Conditional Sigma Factor Expression, Using the Inducible Acetamidase Promoter, Reveals that the Mycobacterium tuberculosis sigF Gene Modulates Expression of the 16-Kilodalton Alpha-Crystallin Homologue

Manabe, Yukari C., Chen, Jong Min, Ko, Chiew G., Chen, Ping, Bishai, William R.

A chemically inducible acetamidase promoter-sigF fusion gene was integrated into the chromosome of Mycobacterium bovis BCG. Two-dimensional protein gel analysis permitted the identification of a...

Virulence of Mycobacterium tuberculosis CDC1551 and H37Rv in Rabbits Evaluated by Lurie’s Pulmonary Tubercle Count Method

Bishai, William R., Dannenberg, Arthur M., Parrish, Nikki, Ruiz, Rafael, Chen, Ping, Zook, Bernard C., ...

The virulence of the CDC1551 strain of Mycobacterium tuberculosis was compared to that of H37Rv in a rabbit inhalation model. While rabbits that inhaled the two strains produced equal numbers of...

Construction and Characterization of a Mycobacterium tuberculosis Mutant Lacking the Alternate Sigma Factor Gene, sigF

Chen, Ping, Ruiz, Rafael E., Li, Qing, Silver, Richard F., Bishai, William R.

The alternate RNA polymerase sigma factor gene, sigF, which is expressed in stationary phase and under stress conditions in vitro, has been deleted in the virulent CDC1551 strain of Mycobacterium...

Novel Selection for Isoniazid (INH) Resistance Genes Supports a Role for NAD+-Binding Proteins in Mycobacterial INH Resistance

Chen, Ping, Bishai, William R.

The genetic basis of isoniazid (INH) resistance remains unknown for a significant proportion of clinical isolates. To identify genes which might confer resistance by detoxifying or sequestering INH,...

Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative σ factor, SigH

Kaushal, Deepak, Schroeder, Benjamin G., Tyagi, Sandeep, Yoshimatsu, Tetsuyuki, Scott, Cherise, Ko, Chiew, ...

The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series of adaptive bacterial virulence factors and inappropriate host immune responses...

Naturally Attenuated, Orally Administered Mycobacterium microti as a Tuberculosis Vaccine Is Better than Subcutaneous Mycobacterium bovis BCG

Manabe, Yukari C., Scott, Cherise P., Bishai, William R.

Mycobacterium microti is phylogenetically closely related to Mycobacterium tuberculosis and is a member of that complex of organisms. It is a curved, acid-fast bacillus that is naturally attenuated...

Comparison of C18-Carboxypropylbetaine and Standard N-Acetyl-l-Cysteine-NaOH Processing of Respiratory Specimens for Increasing Tuberculosis Smear Sensitivity in Brazil

Scott, Cherise P., Dos Anjos Filho, Luciano, De Queiroz Mello, Fernanda Carvalho, Thornton, Charles G., Bishai, William R., Fonseca, Leila S., ...

Techniques to improve the sensitivity of smear microscopy would facilitate early tuberculosis (TB) diagnosis and disease control, especially in low-income countries where the positive predictive...

Field Evaluation of a Rapid Immunochromatographic Test for Tuberculosis

Gounder, Celine, De Queiroz Mello, Fernanda Carvalho, Conde, Marcus B., Bishai, William R., Kritski, Afrânio L., Chaisson, Richard E., ...

Rapid diagnostic tests for tuberculosis (TB) are needed to facilitate early treatment of TB and prevention of Mycobacterium tuberculosis transmission. The ICT Tuberculosis test is a rapid, card-based...

Isolation of Acid-Inducible Genes of Mycobacterium tuberculosis with the Use of Recombinase-Based In Vivo Expression Technology

Saviola, Beatrice, Woolwine, Samuel C., Bishai, William R.

A better understanding of mycobacterial gene regulation under certain stress conditions (e.g., low pH) may provide insight into mechanisms of adaptation during infection. To identify mycobacterial...

Characterization of the Role of the Divalent Metal Ion-Dependent Transcriptional Repressor MntR in the Virulence of Staphylococcus aureus

Ando, Masaru, Manabe, Yukari C., Converse, Paul J., Miyazaki, Eishi, Harrison, Robert, Murphy, John R., ...

DtxR-type metal ion-dependent repressors, present in many bacterial pathogens, may regulate expression of virulence genes such as that encoding diphtheria toxin. SirR, a DtxR homologue initially...

Performance of the Microscopic Observation Drug Susceptibility Assay in Drug Susceptibility Testing for Mycobacterium tuberculosis

Park, Walter G., Bishai, William R., Chaisson, Richard E., Dorman, Susan E.

The drug susceptibility testing performance of a broth-based method with microscopic reading of bacillary growth, the microscopic observation drug susceptibility (MODS) assay, was compared to that of...

A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: Application to Mycobacterium tuberculosis

Lamichhane, Gyanu, Zignol, Matteo, Blades, Natalie J., Geiman, Deborah E., Dougherty, Annette, Grosset, Jacques, ...

We describe a postgenomic in silico approach for identifying genes that are likely to be essential and estimate their proportion in haploid genomes. With the knowledge of all sites eligible for...

Different Strains of Mycobacterium tuberculosis Cause Various Spectrums of Disease in the Rabbit Model of Tuberculosis

Manabe, Yukari C., Dannenberg, Arthur M., Tyagi, Sandeep K., Hatem, Christine L., Yoder, Mark, Woolwine, Samuel C., ...

The rabbit model of tuberculosis has been used historically to differentiate between Mycobacterium tuberculosis and Mycobacterium bovis based on their relative virulence in this animal host. M....

Deletion of Mycobacterium tuberculosis Sigma Factor E Results in Delayed Time to Death with Bacterial Persistence in the Lungs of Aerosol-Infected Mice

Ando, Masaru, Yoshimatsu, Tetsuyuki, Ko, Chiew, Converse, Paul J., Bishai, William R.

The stress-induced extracytoplasmic sigma factor E (SigE) of Mycobacterium tuberculosis shows increased expression after heat shock, sodium dodecyl sulfate treatment, and oxidative stress, as well as...

Susceptibility to Tuberculosis: Clues from Studies with Inbred and Outbred New Zealand White Rabbits

Dorman, Susan E., Hatem, Christine L., Tyagi, Sandeep, Aird, Katherine, Lopez-Molina, Javier, Pitt, M. Louise M., ...

The rabbit model of tuberculosis (TB) is important because rabbits develop a disease that is similar to TB in humans, namely, granulomas with caseous necrosis, liquefaction, and cavities. We describe...

Attenuation of Late-Stage Disease in Mice Infected by the Mycobacterium tuberculosis Mutant Lacking the SigF Alternate Sigma Factor and Identification of SigF-Dependent Genes by Microarray Analysis

Geiman, Deborah E., Kaushal, Deepak, Ko, Chiew, Tyagi, Sandeep, Manabe, Yukari C., Schroeder, Benjamin G., ...

The Mycobacterium tuberculosis alternate sigma factor, SigF, is expressed during stationary growth phase and under stress conditions in vitro. To better understand the function of SigF we studied the...

Method to integrate multiple plasmids into the mycobacterial chromosome

Saviola, Beatrice, Bishai, William R.

In order to create a system in which two independent plasmids can be integrated into a mycobacterial chromosome, a mycobacterial plasmid was constructed containing the phage attachment site attP from...

Modeling In Vivo Pharmacokinetics and Pharmacodynamics of Moxifloxacin Therapy for Mycobacterium tuberculosis Infection by Using a Novel Cartridge System

Ginsburg, Amy Sarah, Lee, Jin, Woolwine, Samuel C., Grosset, Jacques H., Hamzeh, Fayez M., Bishai, William R.

To study the efficacy of moxifloxacin treatment for tuberculosis, we utilized a novel cartridge system to simulate in vivo pharmacokinetics. We found this system to be a robust method for modeling in...

Designer Arrays for Defined Mutant Analysis To Detect Genes Essential for Survival of Mycobacterium tuberculosis in Mouse Lungs

Lamichhane, Gyanu, Tyagi, Sandeep, Bishai, William R.

The mechanisms by which Mycobacterium tuberculosis elicits disease are complex, involving a large repertoire of bacterial genes that are required for in vivo growth and survival. To identify such...

Emergence of Fluoroquinolone Resistance in Mycobacterium tuberculosis during Continuously Dosed Moxifloxacin Monotherapy in a Mouse Model

Ginsburg, Amy Sarah, Sun, Ronggai, Calamita, Heather, Scott, Cherise P., Bishai, William R., Grosset, Jacques H.

Fluoroquinolone resistance in tuberculosis may rapidly emerge. Mice infected with high titers of aerosolized Mycobacterium tuberculosis and treated for 8 weeks with four concentrations of...

Differential Gene Expression in Response to Exposure to Antimycobacterial Agents and Other Stress Conditions among Seven Mycobacterium tuberculosis whiB-Like Genes

Geiman, Deborah E., Raghunand, Tirumalai R., Agarwal, Nisheeth, Bishai, William R.

The seven Mycobacterium tuberculosis whiB-like genes encode small proteins postulated to be transcriptional regulators. A systematic real-time reverse transcription-PCR analysis following exposure to...

Combination Chemotherapy with the Nitroimidazopyran PA-824 and First-Line Drugs in a Murine Model of Tuberculosis†

Nuermberger, Eric, Rosenthal, Ian, Tyagi, Sandeep, Williams, Kathy N., Almeida, Deepak, Peloquin, Charles A., ...

The creation of new chemotherapeutic regimens that permit shortening the duration of treatment is a major priority for antituberculosis drug development. In this study, we used the murine model of...

Mapping Essential Domains of Mycobacterium smegmatis WhmD: Insights into WhiB Structure and Function

Raghunand, Tirumalai R., Bishai, William R.

A growing body of evidence suggests that the WhiB-like proteins exclusive to the GC-rich actinomycete genera play significant roles in pathogenesis and cell division. Each of these proteins contains...

Characterization of the Mycobacterium tuberculosis Sigma Factor SigM by Assessment of Virulence and Identification of SigM-Dependent Genes▿

Agarwal, Nisheeth, Woolwine, Samuel C., Tyagi, Sandeep, Bishai, William R.

Alternate sigma factors have been implicated in the survival of mycobacteria in response to specific stresses. To characterize the role of SigM in Mycobacterium tuberculosis, a sigM deletion mutant...

Mycobacterium tuberculosis SigF Regulates Genes Encoding Cell Wall-Associated Proteins and Directly Regulates the Transcriptional Regulatory Gene phoY1▿ †

Williams, Ernest P., Lee, Jong-Hee, Bishai, William R., Colantuoni, Carlo, Karakousis, Petros C.

Mycobacterium tuberculosis SigF is homologous to stress response and sporulation sigma factors in many bacteria. Consistent with a possible role in mycobacterial survival under stress conditions, M....

Daily Dosing of Rifapentine Cures Tuberculosis in Three Months or Less in the Murine Model

Rosenthal, Ian M, Zhang, Ming, Williams, Kathy N, Peloquin, Charles A, Tyagi, Sandeep, Vernon, Andrew A, ...

Eric Nuermberger and colleagues found that after two months of treatment, mice with lung cultures positive for tuberculosis that received daily doses of rifapentine- and moxifloxacin-containing...

Dormancy Phenotype Displayed by Extracellular Mycobacterium tuberculosis within Artificial Granulomas in Mice

Karakousis, Petros C., Yoshimatsu, Tetsuyuki, Lamichhane, Gyanu, Woolwine, Samuel C., Nuermberger, Eric L., Grosset, Jacques, ...

Mycobacterium tuberculosis residing within pulmonary granulomas and cavities represents an important reservoir of persistent organisms during human latent tuberculosis infection. We present a novel...

In Vivo Validation of the Mutant Selection Window Hypothesis with Moxifloxacin in a Murine Model of Tuberculosis▿

Almeida, Deepak, Nuermberger, Eric, Tyagi, Sandeep, Bishai, William R., Grosset, Jacques

Combination therapy is the most effective strategy to prevent emergence of resistance during tuberculosis (TB) treatment. Another strategy, albeit theoretical, is to limit the time that drug...

Roles of SigB and SigF in the Mycobacterium tuberculosis Sigma Factor Network▿ †

Lee, Jong-Hee, Karakousis, Petros C., Bishai, William R.

To characterize the roles of SigB and SigF in sigma factor regulation in Mycobacterium tuberculosis, we used chemically inducible recombinant strains to conditionally overexpress sigB and sigF. Using...

Role of Stress Response Sigma Factor SigG in Mycobacterium tuberculosis▿ †

Lee, Jong-Hee, Geiman, Deborah E., Bishai, William R.

The sigG gene of Mycobacterium tuberculosis was disrupted by homologous recombination, and the genes regulated by SigG were examined by real-time reverse-transcription PCR and microarray studies. The...

Potent Twice-Weekly Rifapentine-containing Regimens in Murine Tuberculosis

Rosenthal, Ian M., Williams, Kathy, Tyagi, Sandeep, Peloquin, Charles A., Vernon, Andrew A., Bishai, William R., ...

Rationale: Recent studies have demonstrated that intermittent administration of rifamycin-based regimens results in higher rates of tuberculosis relapse and treatment failure compared with daily...

Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model

Nuermberger, Eric, Tyagi, Sandeep, Williams, Kathy N., Rosenthal, Ian, Bishai, William R., Grosset, Jacques H.

Rationale: Priorities for developing improved regimens for treatment of latent tuberculosis (TB) infection include (1) developing shorter and/or more intermittently administered regimens that are...

Extrapulmonary Dissemination of Mycobacterium bovis but Not Mycobacterium tuberculosis in a Bronchoscopic Rabbit Model of Cavitary Tuberculosis▿

Nedeltchev, Gueno G., Raghunand, Tirumalai R., Jassal, Mandeep S., Lun, Shichun, Cheng, Qi-Jian, Bishai, William R.

The rabbit model of tuberculosis is attractive because of its pathophysiologic resemblance to the disease in humans. Rabbits are naturally resistant to infection but may manifest cavitary lung...

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

Maloney, Erin, Stankowska, Dorota, Zhang, Jian, Fol, Marek, Cheng, Qi-Jian, Lun, Shichun, ...

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside...

Weekly Moxifloxacin and Rifapentine Is More Active Than the Denver Regimen in Murine Tuberculosis

Rosenthal, Ian M., Williams, Kathy, Tyagi, Sandeep, Vernon, Andrew A., Peloquin, Charles A., Bishai, William R., ...

Rationale: Treatment of tuberculosis with an efficacious once-weekly regimen would be a significant achievement in improving patient adherence. Currently, the only recommended once-weekly...

Role of the dosR-dosS Two-Component Regulatory System in Mycobacterium tuberculosis Virulence in Three Animal Models▿ †

Converse, Paul J., Karakousis, Petros C., Klinkenberg, Lee G., Kesavan, Anup K., Ly, Lan H., Allen, Shannon Sedberry, ...

The Mycobacterium tuberculosis dosR gene (Rv3133c) is part of an operon, Rv3134c-Rv3132c, and encodes a response regulator that has been shown to be upregulated by hypoxia and other in vitro stress...