William M. Shafer

Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Due to mtrR Mutations

Zarantonelli, Leticia, Borthagaray, Graciela, Lee, Eun-Hee, Shafer, William M.

Single-dose azithromycin therapy has recently been used in Uruguay for the treatment of uncomplicated gonococcal infections. As part of an active surveillance study to monitor the emergence of...

A Putatively Phase Variable Gene (dca) Required for Natural Competence in Neisseria gonorrhoeae but Not Neisseria meningitidis Is Located within the Division Cell Wall (dcw) Gene Cluster

Snyder, Lori A. S., Saunders, Nigel J., Shafer, William M.

A cluster of 18 open reading frames (ORFs), 15 of which are homologous to genes involved in division and cell wall synthesis, has been identified in Neisseria gonorrhoeae and Neisseria meningitidis....

Inducible, but Not Constitutive, Resistance of Gonococci to Hydrophobic Agents Due to the MtrC-MtrD-MtrE Efflux Pump Requires TonB-ExbB-ExbD Proteins

Rouquette-Loughlin, Corinne, Stojiljkovic, Igor, Hrobowski, Tara, Balthazar, Jacqueline T., Shafer, William M.

The MtrC-MtrD-MtrE efflux pump possessed by Neisseria gonorrhoeae is very similar to the MexA-MexB-OprM efflux pump of Pseudomonas aeruginosa. Because the antimicrobial resistance property afforded...

Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae

Veal, Wendy L., Nicholas, Robert A., Shafer, William M.

The importance of the mtrCDE-encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains of Neisseria gonorrhoeae was determined by using genetic derivatives of...

The NorM Efflux Pump of Neisseria gonorrhoeae and Neisseria meningitidis Recognizes Antimicrobial Cationic Compounds

Rouquette-Loughlin, Corinne, Dunham, Steven A., Kuhn, Michael, Balthazar, Jacqueline T., Shafer, William M.

In Neisseria gonorrhoeae and Neisseria meningitidis, we identified a gene that would encode a protein highly similar to NorM of Vibrio parahaemolyticus (Y. Morita et al., Antimicrob. Agents...

The Major Cold Shock Gene, cspA, Is Involved in the Susceptibility of Staphylococcus aureus to an Antimicrobial Peptide of Human Cathepsin G

Katzif, Samuel, Danavall, Damien, Bowers, Samera, Balthazar, Jacqueline T., Shafer, William M.

A Tn551 insertional library of Staphylococcus aureus strain ISP479 was challenged with an antimicrobial peptide (CG 117-136) derived from human neutrophil cathepsin G (CG). After repeated selection...

A Gonococcal Efflux Pump System Enhances Bacterial Survival in a Female Mouse Model of Genital Tract Infection

Jerse, Ann E., Sharma, Nirmala D., Simms, Amy N., Crow, Emily T., Snyder, Lori A., Shafer, William M.

Active efflux of antimicrobial substances is likely to be an important bacterial defense against inhibitory host factors inherent to different body sites. Two well-characterized multidrug resistance...

A Mutant Form of the Neisseria gonorrhoeae Pilus Secretin Protein PilQ Allows Increased Entry of Heme and Antimicrobial Compounds†

Chen, Ching-ju, Tobiason, Deborah M., Thomas, Christopher E., Shafer, William M., Seifert, H. Steven, Sparling, P. Frederick

A spontaneous point mutation in pilQ (pilQ1) resulted in phenotypic suppression of a hemoglobin (Hb) receptor mutant (hpuAB mutant), allowing gonococci to grow on Hb as the sole source of iron. PilQ,...

The Down-Regulation of Cathepsin G in THP-1 Monocytes after Infection with Mycobacterium tuberculosis Is Associated with Increased Intracellular Survival of Bacilli

Rivera-Marrero, Carlos A., Stewart, Julie, Shafer, William M., Roman, Jesse

Cathepsin G (CatG) is a serine protease found in the azurophilic granules of monocytes that is known to have antimicrobial properties, but its role in Mycobacterium tuberculosis infection is unknown....

Regulation of mtrF Expression in Neisseria gonorrhoeae and Its Role in High-Level Antimicrobial Resistance

Folster, Jason P., Shafer, William M.

The obligate human pathogen Neisseria gonorrhoeae uses the MtrC-MtrD-MtrE efflux pump to resist structurally diverse hydrophobic antimicrobial agents (HAs), some of which bathe mucosal surfaces that...

Characterization of the Multiple Transferable Resistance Repressor, MtrR, from Neisseria gonorrhoeae

Hoffmann, Katherine M., Williams, Daniel, Shafer, William M., Brennan, Richard G.

MtrR represses expression of the Neisseria gonorrhoeae mtrCDE multidrug efflux transporter genes. MtrR displays salt-dependent DNA binding, a stoichiometry of two dimers per DNA site, and, for a...

Cationic Antimicrobial Peptide Resistance in Neisseria meningitidis

Tzeng, Yih-Ling, Ambrose, Karita D., Zughaier, Susu, Zhou, Xiaoliu, Miller, Yoon K., Shafer, William M., ...

Cationic antimicrobial peptides (CAMPs) are important components of the innate host defense system against microbial infections and microbial products. However, the human pathogen Neisseria...

Resistance of Neisseria meningitidis to the Toxic Effects of Heme Iron and Other Hydrophobic Agents Requires Expression of ght

Rasmussen, Andrew W., Alexander, Heather L., Perkins-Balding, Donna, Shafer, William M., Stojiljkovic, Igor

Several genetic systems that allow the use of iron-protoporphyrin IX (heme) have been described for the pathogenic bacterium Neisseria meningitidis. However, many questions about the process of heme...

CspA Regulates Pigment Production in Staphylococcus aureus through a SigB-Dependent Mechanism

Katzif, Samuel, Lee, Eun-Hee, Law, Anthony B., Tzeng, Yih-Ling, Shafer, William M.

We report that the cold shock protein CspA of Staphylococcus aureus is required for maximal production of pigment. Results from transcriptional studies revealed that loss of CspA resulted in...

Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophages

Zughaier, Susu M., Shafer, William M., Stephens, David S.

Antimicrobial peptides (AMPs), in addition to their antibacterial properties, are also chemotactic and signalling molecules that connect the innate and adaptive immune responses. The role of AMP [α...

Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Due to mtrR Mutations

Zarantonelli, Leticia, Borthagaray, Graciela, Lee, Eun-Hee, Shafer, William M.

Single-dose azithromycin therapy has recently been used in Uruguay for the treatment of uncomplicated gonococcal infections. As part of an active surveillance study to monitor the emergence of...

A Putatively Phase Variable Gene (dca) Required for Natural Competence in Neisseria gonorrhoeae but Not Neisseria meningitidis Is Located within the Division Cell Wall (dcw) Gene Cluster

Snyder, Lori A. S., Saunders, Nigel J., Shafer, William M.

A cluster of 18 open reading frames (ORFs), 15 of which are homologous to genes involved in division and cell wall synthesis, has been identified in Neisseria gonorrhoeae and Neisseria meningitidis....

Inducible, but Not Constitutive, Resistance of Gonococci to Hydrophobic Agents Due to the MtrC-MtrD-MtrE Efflux Pump Requires TonB-ExbB-ExbD Proteins

Rouquette-Loughlin, Corinne, Stojiljkovic, Igor, Hrobowski, Tara, Balthazar, Jacqueline T., Shafer, William M.

The MtrC-MtrD-MtrE efflux pump possessed by Neisseria gonorrhoeae is very similar to the MexA-MexB-OprM efflux pump of Pseudomonas aeruginosa. Because the antimicrobial resistance property afforded...

Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae

Veal, Wendy L., Nicholas, Robert A., Shafer, William M.

The importance of the mtrCDE-encoded efflux pump in conferring chromosomally mediated penicillin resistance on certain strains of Neisseria gonorrhoeae was determined by using genetic derivatives of...

The NorM Efflux Pump of Neisseria gonorrhoeae and Neisseria meningitidis Recognizes Antimicrobial Cationic Compounds

Rouquette-Loughlin, Corinne, Dunham, Steven A., Kuhn, Michael, Balthazar, Jacqueline T., Shafer, William M.

In Neisseria gonorrhoeae and Neisseria meningitidis, we identified a gene that would encode a protein highly similar to NorM of Vibrio parahaemolyticus (Y. Morita et al., Antimicrob. Agents...

The Major Cold Shock Gene, cspA, Is Involved in the Susceptibility of Staphylococcus aureus to an Antimicrobial Peptide of Human Cathepsin G

Katzif, Samuel, Danavall, Damien, Bowers, Samera, Balthazar, Jacqueline T., Shafer, William M.

A Tn551 insertional library of Staphylococcus aureus strain ISP479 was challenged with an antimicrobial peptide (CG 117-136) derived from human neutrophil cathepsin G (CG). After repeated selection...

A Gonococcal Efflux Pump System Enhances Bacterial Survival in a Female Mouse Model of Genital Tract Infection

Jerse, Ann E., Sharma, Nirmala D., Simms, Amy N., Crow, Emily T., Snyder, Lori A., Shafer, William M.

Active efflux of antimicrobial substances is likely to be an important bacterial defense against inhibitory host factors inherent to different body sites. Two well-characterized multidrug resistance...

A Mutant Form of the Neisseria gonorrhoeae Pilus Secretin Protein PilQ Allows Increased Entry of Heme and Antimicrobial Compounds†

Chen, Ching-ju, Tobiason, Deborah M., Thomas, Christopher E., Shafer, William M., Seifert, H. Steven, Sparling, P. Frederick

A spontaneous point mutation in pilQ (pilQ1) resulted in phenotypic suppression of a hemoglobin (Hb) receptor mutant (hpuAB mutant), allowing gonococci to grow on Hb as the sole source of iron. PilQ,...

The Down-Regulation of Cathepsin G in THP-1 Monocytes after Infection with Mycobacterium tuberculosis Is Associated with Increased Intracellular Survival of Bacilli

Rivera-Marrero, Carlos A., Stewart, Julie, Shafer, William M., Roman, Jesse

Cathepsin G (CatG) is a serine protease found in the azurophilic granules of monocytes that is known to have antimicrobial properties, but its role in Mycobacterium tuberculosis infection is unknown....

Regulation of mtrF Expression in Neisseria gonorrhoeae and Its Role in High-Level Antimicrobial Resistance

Folster, Jason P., Shafer, William M.

The obligate human pathogen Neisseria gonorrhoeae uses the MtrC-MtrD-MtrE efflux pump to resist structurally diverse hydrophobic antimicrobial agents (HAs), some of which bathe mucosal surfaces that...

Characterization of the Multiple Transferable Resistance Repressor, MtrR, from Neisseria gonorrhoeae

Hoffmann, Katherine M., Williams, Daniel, Shafer, William M., Brennan, Richard G.

MtrR represses expression of the Neisseria gonorrhoeae mtrCDE multidrug efflux transporter genes. MtrR displays salt-dependent DNA binding, a stoichiometry of two dimers per DNA site, and, for a...

Cationic Antimicrobial Peptide Resistance in Neisseria meningitidis

Tzeng, Yih-Ling, Ambrose, Karita D., Zughaier, Susu, Zhou, Xiaoliu, Miller, Yoon K., Shafer, William M., ...

Cationic antimicrobial peptides (CAMPs) are important components of the innate host defense system against microbial infections and microbial products. However, the human pathogen Neisseria...

Resistance of Neisseria meningitidis to the Toxic Effects of Heme Iron and Other Hydrophobic Agents Requires Expression of ght

Rasmussen, Andrew W., Alexander, Heather L., Perkins-Balding, Donna, Shafer, William M., Stojiljkovic, Igor

Several genetic systems that allow the use of iron-protoporphyrin IX (heme) have been described for the pathogenic bacterium Neisseria meningitidis. However, many questions about the process of heme...

CspA Regulates Pigment Production in Staphylococcus aureus through a SigB-Dependent Mechanism

Katzif, Samuel, Lee, Eun-Hee, Law, Anthony B., Tzeng, Yih-Ling, Shafer, William M.

We report that the cold shock protein CspA of Staphylococcus aureus is required for maximal production of pigment. Results from transcriptional studies revealed that loss of CspA resulted in...

Differential Regulation of ponA and pilMNOPQ Expression by the MtrR Transcriptional Regulatory Protein in Neisseria gonorrhoeae▿

Folster, Jason P., Dhulipala, Vijaya, Nicholas, Robert A., Shafer, William M.

Neisseria gonorrhoeae utilizes the mtrCDE-encoded efflux pump system to resist not only host-derived, hydrophobic antimicrobials that bathe mucosal surfaces, which likely aids in its ability to...

Two ABC Transporter Operons and the Antimicrobial Resistance Gene mtrF Are pilT Responsive in Neisseria gonorrhoeae▿

Friedrich, Alexandra, Arvidson, Cindy G., Shafer, William M., Lee, Eun-Hee, So, Magdalene

Retraction of type IV pili is mediated by PilT. We show that loss of pilT function leads to upregulation of mtrF (multiple transferable resistance) and two operons encoding putative ABC transporters...

The TolC-Like Protein of Neisseria meningitidis Is Required for Extracellular Production of the Repeats-in-Toxin Toxin FrpC but Not for Resistance to Antimicrobials Recognized by the Mtr Efflux Pump System▿

Kamal, Nazia, Rouquette-Loughlin, Corinne, Shafer, William M.

A 2.9-kilobase pair locus in Neisseria meningitidis was identified as containing transcriptionally linked open reading frames encoding TolC- and HlyD-like proteins. Although the meningococcal TolC...