Research Topics
| William ShaferSummaryAffiliation: Emory University Country: USA Publications
Research Grants
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Detail Information
Publications
Inducible, but not constitutive, resistance of gonococci to hydrophobic agents due to the MtrC-MtrD-MtrE efflux pump requires TonB-ExbB-ExbD proteinsCorinne Rouquette-Loughlin
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Antimicrob Agents Chemother 46:561-5. 2002....- MpeR regulates the mtr efflux locus in Neisseria gonorrhoeae and modulates antimicrobial resistance by an iron-responsive mechanismAlexandra Dubon Mercante
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
Antimicrob Agents Chemother 56:1491-501. 2012..Collectively, our results indicate that both genetic and physiologic parameters (e.g., iron availability) can influence the expression of the mtr efflux system and modulate levels of gonococcal susceptibility to efflux pump substrates... - Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump familyW M Shafer
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Proc Natl Acad Sci U S A 95:1829-33. 1998..These results indicate that such efflux systems may enable mucosal pathogens like gonococci to resist endogenous antimicrobial peptides that are thought to act during infection... 
Genetic organization and regulation of antimicrobial efflux systems possessed by Neisseria gonorrhoeae and Neisseria meningitidisW M Shafer
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Mol Microbiol Biotechnol 3:219-24. 2001..The overriding theme of this review is that the efflux pumps possessed by these pathogens likely contribute to their pathogenic mechanisms by providing a means to escape a number of antimicrobial compounds that bathe mucosal surfaces...- Towards an understanding of chromosomally mediated penicillin resistance in Neisseria gonorrhoeae: evidence for a porin-efflux pump collaborationWilliam M Shafer
Laboratory of Bacterial Pathogenesis, Room 5A181, VA Medical Center, Decatur, GA 30033, USA
J Bacteriol 188:2297-9. 2006 - Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogensW M Shafer
Laboratories of Bacterial Pathogenesis, Research Service, The VA Medical Center, Decatur, GA 30033, USA
Curr Pharm Des 8:695-702. 2002..This approach could prove beneficial to those interested in developing antimicrobial peptides as therapeutic agents... - Phase variable changes in genes lgtA and lgtC within the lgtABCDE operon of Neisseria gonorrhoeae can modulate gonococcal susceptibility to normal human serumWilliam M Shafer
Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center Atlanta, Decatur, Georgia 30333, USA
J Endotoxin Res 8:47-58. 2002..Hence, phase variation within the lgtABCDE operon can significantly impact the ability of gonococci to subvert this important host defense system... - Taking the gonococcus-human relationship to a whole new level: implications for the coevolution of microbes and humansWilliam M Shafer
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA
MBio 2:e00067-11. 2011..While the function of this element in gonococci remains unclear, this finding significantly impacts our consideration of the coevolution of hosts and microbes, particularly that of humans and pathogens... - Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrD-MtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitnessDouglas M Warner
Department of Microbiology and Immunology, F Edward Hebert School of Medicine, Uniformed Services University, Bethesda, MD, USA
Mol Microbiol 70:462-78. 2008..These studies establish a hierarchy of mtrR locus mutations with regard to regulation of pump efflux, and suggest selection for more derepressed mutants may occur during mixed infections... - Overexpression of the MtrC-MtrD-MtrE efflux pump due to an mtrR mutation is required for chromosomally mediated penicillin resistance in Neisseria gonorrhoeaeWendy L Veal
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Bacteriol 184:5619-24. 2002.... - Regulation of the MtrC-MtrD-MtrE efflux-pump system modulates the in vivo fitness of Neisseria gonorrhoeaeDouglas M Warner
Department of Microbiology and Immunology, F Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20853, USA
J Infect Dis 196:1804-12. 2007.... - The major cold shock gene, cspA, is involved in the susceptibility of Staphylococcus aureus to an antimicrobial peptide of human cathepsin GSamuel Katzif
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Infect Immun 71:4304-12. 2003..The results indicate for the first time that a physiologic link exists between bacterial susceptibility to an antimicrobial peptide and a stress response system... - Cationic antimicrobial peptide resistance in Neisseria meningitidisYih Ling Tzeng
Department of Veterans Affairs Medical Center, Research 151, Room 5A188, 1670 Clairmont Road, Decatur, GA 30033, USA
J Bacteriol 187:5387-96. 2005..The modification of meningococcal lipid A head groups with PEA also prevents neutralization of the biological effects of endotoxin by CAMP... - Characterization of the MacA-MacB efflux system in Neisseria gonorrhoeaeCorinne E Rouquette-Loughlin
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Antimicrob Chemother 56:856-60. 2005.... - Regulation of mtrF expression in Neisseria gonorrhoeae and its role in high-level antimicrobial resistanceJason P Folster
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Bacteriol 187:3713-20. 2005..In addition to MtrR, another repressor (MpeR) can downregulate the expression of mtrF. Repression of mtrF by MtrR and MpeR was additive, demonstrating that the repressive effects mediated by these regulators are independent processes... - Differential regulation of ponA and pilMNOPQ expression by the MtrR transcriptional regulatory protein in Neisseria gonorrhoeaeJason P Folster
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Bacteriol 189:4569-77. 2007.... - A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infectionAnn E Jerse
Department of Microbiology and Immunology, F Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
Infect Immun 71:5576-82. 2003..However, hormonally regulated factors rather than progesterone itself may be responsible for the more rapid clearance of mtr-deficient gonococci from intact mice... - Integration Host Factor is required for FarR repression of the farAB-encoded efflux pump of Neisseria gonorrhoeaeEun-Hee Lee
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Mol Microbiol 60:1381-400. 2006..We propose a model in which expression of the farAB-encoded efflux pump in N. gonorrhoeae is modulated by the DNA binding activities of FarR and IHF... - 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 systemNazia Kamal
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Infect Immun 75:6008-12. 2007.... - MtrR modulates rpoH expression and levels of antimicrobial resistance in Neisseria gonorrhoeaeJason P Folster
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Bacteriol 191:287-97. 2009..g., antimicrobial peptides) recognized by the efflux pump, the ability of MtrR to regulate the expression levels of rpoH and RpoH-regulated genes also modulates levels of gonococcal susceptibility to H(2)O(2)... - Antimicrobial peptides and endotoxin inhibit cytokine and nitric oxide release but amplify respiratory burst response in human and murine macrophagesSusu M Zughaier
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, and Laboratories of Microbial Pathogenesis, Atlanta, GA, USA
Cell Microbiol 7:1251-62. 2005.... - The human host defense peptide LL-37 interacts with Neisseria meningitidis capsular polysaccharides and inhibits inflammatory mediators releaseSusu M Zughaier
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine and Laboratories of Microbial Pathogenesis, Atlanta, Georgia, United States of America
PLoS ONE 5:e13627. 2010..We conclude that the capacity of meningococcal CPS to activate macrophages via TLR2 and TLR4-MD-2 can be inhibited by the human cationic host defense peptide LL-37 and propose that this impacts CPS-based vaccine responses... - Resistance of neisseria meningitidis to the toxic effects of heme iron and other hydrophobic agents requires expression of ghtAndrew W Rasmussen
Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd NE, Atlanta, GA 30322, USA
J Bacteriol 187:5214-23. 2005..We present genetic evidence for the importance of ght in resistance to hydrophobic agents and its potential role in interaction with other hydrophobic agent resistance mechanisms within N. meningitidis... - Identification of a cell envelope protein (MtrF) involved in hydrophobic antimicrobial resistance in Neisseria gonorrhoeaeWendy L Veal
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Antimicrob Chemother 51:27-37. 2003..We propose that MtrF acts in conjunction with the MtrC-MtrD-MtrE efflux pump, to confer on gonococci high-level resistance to certain HAs... - The down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilliCarlos A Rivera-Marrero
Department of Medicine, Pulmonary, Allergy and Critical Care Division, Emory University School of Medicine, Atlanta, Georgia, USA
Infect Immun 72:5712-21. 2004..tuberculosis bacilli more viable. Therefore, the down-regulation of CatG in macrophages is advantageous to M. tuberculosis bacilli and possibly is an important mechanism by which M. tuberculosis is able to evade the host immune defenses... - Modulation of the mtrCDE-encoded efflux pump gene complex of Neisseria meningitidis due to a Correia element insertion sequenceCorinne E Rouquette-Loughlin
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Mol Microbiol 54:731-41. 2004..We conclude that the mtr efflux system in meningococci is subject to transcriptional regulation by IHF and post-transcriptional regulation by cleavage in the inverted repeat of the Correia element... - Phenotypic and genotypic analyses of Neisseria gonorrhoeae isolates that express frequently recovered PorB PIA variable region types suggest that certain P1a porin sequences confer a selective advantage for urogenital tract infectionLotisha E Garvin
Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20853 4799, USA
Infect Immun 76:3700-9. 2008..The capacity of some porin types to evade a porin-specific adaptive immune response must also be considered... - Biologic activities of the TolC-like protein of Neisseria meningitidis as assessed by functional complementation in Escherichia coliNazia Kamal
Department of Microbiology, Emory University School of Medicine, Atlanta, GA 30322, USA
Antimicrob Agents Chemother 54:506-8. 2010..We now report that expression of the meningococcal tolC gene in a TolC-deficient strain of Escherichia coli can restore properties of alpha-hemolysis and antimicrobial resistance known to involve efflux pumps... - Polyamines can increase resistance of Neisseria gonorrhoeae to mediators of the innate human host defenseMaira Goytia
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Infect Immun 78:3187-95. 2010..We propose that polyamines in genital mucosal fluids may enhance gonococcal survival during infection by reducing bacterial susceptibility to host-derived antimicrobials that function in innate host defense... - Altered growth, pigmentation, and antimicrobial susceptibility properties of Staphylococcus aureus due to loss of the major cold shock gene cspBBrea D Duval
Department of Microbiology and Immunology, Research Service VAMC, University School of Medicine, Atlanta, Georgia 30322, USA
Antimicrob Agents Chemother 54:2283-90. 2010..Taken together, our results link a stress response protein (CspB) of S. aureus to important phenotypic properties that include resistance to certain antimicrobials... - The NorM efflux pump of Neisseria gonorrhoeae and Neisseria meningitidis recognizes antimicrobial cationic compoundsCorinne Rouquette-Loughlin
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Bacteriol 185:1101-6. 2003..Structure-activity relationship studies with putative NorM substrates have found that a cationic moiety is essential for NorM recognition... - Susceptibility of Treponema pallidum to host-derived antimicrobial peptidesDavid L Cox
Sexually Transmitted Infections Branch, Division of AIDS, STD and TB Laboratory Research, Center for HIV and STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA
Peptides 24:1741-6. 2003..pallidum. Infectivity of T. pallidum in a rabbit model could effectively be blocked with the synthetic truncated LL-37-derived peptide WS22-N-amide... - CspA regulates pigment production in Staphylococcus aureus through a SigB-dependent mechanismSamuel Katzif
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Bacteriol 187:8181-4. 2005..Results from transcriptional studies revealed that loss of CspA resulted in decreased expression of genes needed for the biosynthesis of 4,4'-diaponeurosporene and the alternative sigma factor SigB... - Human antimicrobial peptide LL-37 induces MefE/Mel-mediated macrolide resistance in Streptococcus pneumoniaeDorothea Zahner
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA
Antimicrob Agents Chemother 54:3516-9. 2010..Such induction may impact the efficacy of host defenses and of macrolide-based treatment of pneumococcal disease... - Off-target gene regulation mediated by transcriptional repressors of antimicrobial efflux pump genes in Neisseria gonorrhoeaePaul J T Johnson
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Antimicrob Agents Chemother 55:2559-65. 2011.... - Functional cloning and characterization of the multidrug efflux pumps NorM from Neisseria gonorrhoeae and YdhE from Escherichia coliFeng Long
Molecular, Cellular, and Developmental Biology Interdepartmental Graduate Program, Iowa State University, Ames, Iowa 50011, USA
Antimicrob Agents Chemother 52:3052-60. 2008.... - Characterization of the multiple transferable resistance repressor, MtrR, from Neisseria gonorrhoeaeKatherine M Hoffmann
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, 97239-3098, USA
J Bacteriol 187:5008-12. 2005..MtrR displays salt-dependent DNA binding, a stoichiometry of two dimers per DNA site, and, for a protein that was expected to be essentially all helical, a high percentage of random coil and possibly beta-sheet structure... - A mutant form of the Neisseria gonorrhoeae pilus secretin protein PilQ allows increased entry of heme and antimicrobial compoundsChing Ju Chen
Department of Medicine Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7031, USA
J Bacteriol 186:730-9. 2004..These results show that PilQ forms a channel that allows entry of heme and certain antimicrobial compounds and that a gain-of function point mutation in pilQ results in TonB-independent, PilT-dependent increase of entry... - Two ABC transporter operons and the antimicrobial resistance gene mtrF are pilT responsive in Neisseria gonorrhoeaeAlexandra Friedrich
Department of Molecular Microbiology and Immunology, L220, Oregon Health Sciences University, Portland, Oregon 97201 3098, USA
J Bacteriol 189:5399-402. 2007..This effect occurs indirectly through the transcriptional regulator FarR, which until now has been shown to regulate only farAB. L-Glutamine can reverse pilT downregulation of the ABC transporter operons and mtrF... - Divergence and transcriptional analysis of the division cell wall (dcw) gene cluster in Neisseria sppLori A S Snyder
The Sir William Dunn School of Pathology, Univrsity of Oxford, South Parks Road, Oxford OX1 3RE, UK
Mol Microbiol 47:431-42. 2003.... - The increased bactericidal activity of a fatty acid-modified synthetic antimicrobial peptide of human cathepsin G correlates with its enhanced capacity to interact with model membranesPawel Mak
Institute of Molecular Biology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland
Int J Antimicrob Agents 21:13-9. 2003.... - Crystallization and preliminary X-ray diffraction analysis of the multidrug efflux transporter NorM from Neisseria gonorrhoeaeChih Chia Su
Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 64:289-92. 2008..The best crystal diffracted anisotropically to 3.8 A and diffraction data were complete to 6.5 A resolution. The space group was determined to be C2, with unit-cell parameters a = 81.5, b = 164.4, c = 111.5 A...
Research Grants
- GONOCOCCI: GENETICS OF RESISTANCE TO PMN PROTEINSWilliam Shafer; Fiscal Year: 2004....
- GONOCOCCI: GENETICS OF RESISTANCE TO PMN PROTEINSWilliam Shafer; Fiscal Year: 2009..abstract_text> ..
- Sexually Transmitted Infections & Antimicrobial PeptidesWilliam Shafer; Fiscal Year: 2009..abstract_text> ..
- DEVELOPMENT OF STAPHYLOCOCCALCIDAL HUMAN PEPTIDESWilliam Shafer; Fiscal Year: 2007..This information should help in the development of new effective peptide-based drugs that could be used in the future to combat staphylococcal diseases caused by antibiotic-resistant strains. ..
- GONOCOCCI--GENETICS OF RESISTANCE TO PMM PROTEINSWilliam Shafer; Fiscal Year: 1999..2) Examine uptake and afflux of HAs using isogenic strains differing in the MtrC, MtrD and MtrE proteins and 3) Define the mechanisms by which the mtr operon is regulated. ..
- DEVELOPMENT OF STAPHYLOCOCCALCIDAL HUMAN PEPTIDESWilliam Shafer; Fiscal Year: 2001....
- GONOCOCCI: GENETICS OF RESISTANCE TO PMN PROTEINSWilliam Shafer; Fiscal Year: 1993....
- GONOCOCCI: GENETICS OF RESISTANCE TO PMN PROTEINSWilliam Shafer; Fiscal Year: 1990..The capacity of cathepsin G to damage the cell envelope and thereby release pharmacologically active peptidoglycan and lipopolysaccharide will be tested since intraphagosomal killing of gonococci may have pathophysiologic consequences...