Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae
Abstract
Neisseria gonorrhoeaeresponds to host-derived antimicrobials by inducing the expression of themtrCDE-encoded multidrug efflux pump, which expels microbicides, such as bile salts, fatty acids, and multiple extrinsically administered drugs, from the cell. In the absence of these cytotoxins, the TetR family member MtrR represses themtrCDEgenes. Although antimicrobial-dependent derepression ofmtrCDEis clear, the physiological inducers of MtrR are unknown. Here, we report the crystal structure of an induced form of MtrR. In the binding pocket of MtrR, we observed electron density that we hypothesized wasN-cyclohexyl-3-aminopropanesulfonic acid (CAPS), a component of the crystallization reagent. Using the MtrR-CAPS structure as an inducer-bound template, we hypothesized that bile salts, which bear significant chemical resemblance to CAPS, are physiologically relevant inducers. Indeed, characterization of MtrR-chenodeoxycholate and MtrR-taurodeoxycholate interactions, bothin vitroandin vivo, revealed that these bile salts, but not glyocholate or taurocholate, bind MtrR tightly and can act as bona fide inducers. Furthermore, two residues, W136 and R176, were shown to be important in binding chenodeoxycholate but not taurodeoxycholate, suggesting different binding modes of the bile salts. These data provide insight into a crucial mechanism utilized by the pathogen to overcome innate human defenses. IMPORTANCENeisseria gonorrhoeaecauses a significant disease burden worldwide, and a meteoric rise in its multidrugmore »
- Authors:
-
[8];
[9];
- Duke Univ., School of Medicine, Durham, NC (United States). Dept. of Biochemistry
- Emory Univ., School of Medicine, Atlanta, GA (United States). Dept. of Microbiology and Immunology; Emory Univ., School of Medicine, Atlanta, GA (United States). Emory Antibiotic Resistance Center
- Baylor College of Medicine, Houston, TX (United States). Dept.of Pharmacology and Chemical Biology; Baylor College of Medicine, Houston, TX (United States). Dept. of Biochemistry and Molecular Biology
- Houston Methodist Hospital Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Univ. of Texas, MD Anderson Cancer Center, Houston, TX (United States). Dept. of Biochemistry and Molecular Biology; Houston Methodist Hospital System, Houston, TX (United States). Dept. of Pathology and Genomic Medicine
- Houston Methodist Hospital Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Hospital System, Houston, TX (United States). Dept. of Pathology and Genomic Medicine
- Baylor College of Medicine, Houston, TX (United States). Dept.of Pharmacology and Chemical Biology; Baylor College of Medicine, Houston, TX (United States). Dept. of Biochemistry and Molecular Biology
- Emory Univ., School of Medicine, Atlanta, GA (United States). Dept. of Microbiology and Immunology; Veterans Affairs Medical Center, Decatur, GA (United States). Laboratories of Microbial Pathogenesis, VA Medical Research Service; Emory Univ., School of Medicine, Atlanta, GA (United States). Dept. of Emory Antibiotic Resistance Center
- Houston Methodist Hospital Research Institute, Houston, TX (United States). Center for Molecular and Translational Human Infectious Diseases Research; Houston Methodist Hospital System, Houston, TX (United States). Dept. of Pathology and Genomic Medicine
- Duke Univ., School of Medicine, Durham, NC (United States). Dept. of Biochemistry
- Rutgers Univ., New Brunswick, NJ (United States)
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division; National Institutes of Health (NIH); National Science Foundation Graduate Research Fellowship
- OSTI Identifier:
- 1626068
- Grant/Contract Number:
- AC03-76SF00098; 1R01AI109096-01A1; R05 AI048593-09; R37 AI021150-32
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Bacteriology
- Additional Journal Information:
- Journal Volume: 201; Journal Issue: 20; Journal ID: ISSN 0021-9193
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- Microbiology; MtrR; Neisseria gonorrhoeaebile; salts; multidrug resistance; repression; structural biology; transcription
Citation Formats
Beggs, Grace A., Zalucki, Yaramah M., Brown, Nicholas Gene, Rastegari, Sheila, Phillips, Rebecca K., Palzkill, Timothy, Shafer, William M., Kumaraswami, Muthiah, Brennan, Richard G., and Stock, Ann M. Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae. United States: N. p., 2019.
Web. doi:10.1128/jb.00401-19.
Beggs, Grace A., Zalucki, Yaramah M., Brown, Nicholas Gene, Rastegari, Sheila, Phillips, Rebecca K., Palzkill, Timothy, Shafer, William M., Kumaraswami, Muthiah, Brennan, Richard G., & Stock, Ann M. Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae. United States. https://doi.org/10.1128/jb.00401-19
Beggs, Grace A., Zalucki, Yaramah M., Brown, Nicholas Gene, Rastegari, Sheila, Phillips, Rebecca K., Palzkill, Timothy, Shafer, William M., Kumaraswami, Muthiah, Brennan, Richard G., and Stock, Ann M. Mon .
"Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae". United States. https://doi.org/10.1128/jb.00401-19. https://www.osti.gov/servlets/purl/1626068.
@article{osti_1626068,
title = {Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae},
author = {Beggs, Grace A. and Zalucki, Yaramah M. and Brown, Nicholas Gene and Rastegari, Sheila and Phillips, Rebecca K. and Palzkill, Timothy and Shafer, William M. and Kumaraswami, Muthiah and Brennan, Richard G. and Stock, Ann M.},
abstractNote = {Neisseria gonorrhoeaeresponds to host-derived antimicrobials by inducing the expression of themtrCDE-encoded multidrug efflux pump, which expels microbicides, such as bile salts, fatty acids, and multiple extrinsically administered drugs, from the cell. In the absence of these cytotoxins, the TetR family member MtrR represses themtrCDEgenes. Although antimicrobial-dependent derepression ofmtrCDEis clear, the physiological inducers of MtrR are unknown. Here, we report the crystal structure of an induced form of MtrR. In the binding pocket of MtrR, we observed electron density that we hypothesized wasN-cyclohexyl-3-aminopropanesulfonic acid (CAPS), a component of the crystallization reagent. Using the MtrR-CAPS structure as an inducer-bound template, we hypothesized that bile salts, which bear significant chemical resemblance to CAPS, are physiologically relevant inducers. Indeed, characterization of MtrR-chenodeoxycholate and MtrR-taurodeoxycholate interactions, bothin vitroandin vivo, revealed that these bile salts, but not glyocholate or taurocholate, bind MtrR tightly and can act as bona fide inducers. Furthermore, two residues, W136 and R176, were shown to be important in binding chenodeoxycholate but not taurodeoxycholate, suggesting different binding modes of the bile salts. These data provide insight into a crucial mechanism utilized by the pathogen to overcome innate human defenses. IMPORTANCENeisseria gonorrhoeaecauses a significant disease burden worldwide, and a meteoric rise in its multidrug resistance has reduced the efficacy of antibiotics previously or currently approved for therapy of gonorrheal infections. The multidrug efflux pump MtrCDE transports multiple drugs and host-derived antimicrobials from the bacterial cell and confers survival advantage on the pathogen within the host. Transcription of the pump is repressed by MtrR but relieved by the cytosolic influx of antimicrobials. Here, we describe the structure of induced MtrR and use this structure to identify bile salts as physiological inducers of MtrR. These findings provide a mechanistic basis for antimicrobial sensing and gonococcal protection by MtrR through the derepression ofmtrCDEexpression after exposure to intrinsic and clinically applied antimicrobials.},
doi = {10.1128/jb.00401-19},
journal = {Journal of Bacteriology},
number = 20,
volume = 201,
place = {United States},
year = {Mon Jul 22 00:00:00 EDT 2019},
month = {Mon Jul 22 00:00:00 EDT 2019}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 10 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Regulation of the MtrC‐MtrD‐MtrE Efflux‐Pump System Modulates the In Vivo Fitness of Neisseria gonorrhoeae
journal, December 2007
- Warner, Douglas M.; Folster, Jason P.; Shafer, William M.
- The Journal of Infectious Diseases, Vol. 196, Issue 12
Antimicrobial Resistance Expressed by Neisseria gonorrhoeae: A Major Global Public Health Problem in the 21st Century
journal, June 2016
- Unemo, Magnus; del Rio, Carlos; Shafer, William M.
- Microbiology Spectrum, Vol. 4, Issue 3
Modification of a PCRBased Site-Directed Mutagenesis Method
journal, October 1997
- Fisher, Constance L.; Pei, Guo Kui
- BioTechniques, Vol. 23, Issue 4
Crystal Structures of Multidrug Binding Protein TtgR in Complex with Antibiotics and Plant Antimicrobials
journal, June 2007
- Alguel, Yilmaz; Meng, Cuixiang; Terán, Wilson
- Journal of Molecular Biology, Vol. 369, Issue 3
The MtrD protein of Neisseria gonorrhoeae is a member of the resistance/nodulation/division protein family constituting part of an efflux system
journal, July 1997
- Nilles, Matthew; Lucas, Claressa E.; Balthazar, Jacqueline T.
- Microbiology, Vol. 143, Issue 7
Structural Mechanisms of QacR Induction and Multidrug Recognition
journal, December 2001
- Schumacher, M. A.
- Science, Vol. 294, Issue 5549
Characterization of the multidrug efflux regulator AcrR from Escherichia coli
journal, September 2007
- Su, Chih-Chia; Rutherford, Denae J.; Yu, Edward W.
- Biochemical and Biophysical Research Communications, Vol. 361, Issue 1
Decreased Azithromycin Susceptibility ofNeisseria gonorrhoeae Due to mtrRMutations
journal, October 1999
- Zarantonelli, Leticia; Borthagaray, Graciela; Lee, Eun-Hee
- Antimicrobial Agents and Chemotherapy, Vol. 43, Issue 10
On the in vivo significance of bacterial resistance to antimicrobial peptides
journal, November 2015
- Bauer, Margaret E.; Shafer, William M.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1848, Issue 11
Bile salts enhance bacterial co-aggregation, bacterial-intestinal epithelial cell adhesion, biofilm formation and antimicrobial resistance of Bacteroides fragilis
journal, August 2007
- Pumbwe, Lilian; Skilbeck, Christopher A.; Nakano, Viviane
- Microbial Pathogenesis, Vol. 43, Issue 2-3
ImageJ2: ImageJ for the next generation of scientific image data
journal, November 2017
- Rueden, Curtis T.; Schindelin, Johannes; Hiner, Mark C.
- BMC Bioinformatics, Vol. 18, Issue 1
Bacterial antibiotic efflux systems of medical importance
journal, December 1999
- K�hler, T.; Pech�re, J. -C.; Pl�siat, P.
- Cellular and Molecular Life Sciences (CMLS), Vol. 56, Issue 9-10
Towards automated crystallographic structure refinement with phenix.refine
journal, March 2012
- Afonine, Pavel V.; Grosse-Kunstleve, Ralf W.; Echols, Nathaniel
- Acta Crystallographica Section D Biological Crystallography, Vol. 68, Issue 4
A Gonococcal Efflux Pump System Enhances Bacterial Survival in a Female Mouse Model of Genital Tract Infection
journal, September 2003
- Jerse, A. E.; Sharma, N. D.; Simms, A. N.
- Infection and Immunity, Vol. 71, Issue 10
Multidrug efflux pumps: structure, function and regulation
journal, July 2018
- Du, Dijun; Wang-Kan, Xuan; Neuberger, Arthur
- Nature Reviews Microbiology, Vol. 16, Issue 9
Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae
journal, March 1998
- Veal, W. L.; Yellen, A.; Balthazar, J. T.
- Microbiology, Vol. 144, Issue 3
Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium
journal, April 2004
- Prouty, A. M.; Brodsky, I. E.; Falkow, S.
- Microbiology, Vol. 150, Issue 4
Crystal Structure of the Neisseria gonorrhoeae MtrD Inner Membrane Multidrug Efflux Pump
journal, June 2014
- Bolla, Jani Reddy; Su, Chih-Chia; Do, Sylvia V.
- PLoS ONE, Vol. 9, Issue 6
electronic Ligand Builder and Optimization Workbench ( eLBOW ): a tool for ligand coordinate and restraint generation
journal, September 2009
- Moriarty, Nigel W.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Acta Crystallographica Section D Biological Crystallography, Vol. 65, Issue 10
Antimicrobial resistance in Neisseria gonorrhoeae: Global surveillance and a call for international collaborative action
journal, July 2017
- Wi, Teodora; Lahra, Monica M.; Ndowa, Francis
- PLOS Medicine, Vol. 14, Issue 7
The CCP4 suite programs for protein crystallography
journal, September 1994
- ,
- Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763
MtrR Modulates rpoH Expression and Levels of Antimicrobial Resistance in Neisseria gonorrhoeae
journal, October 2008
- Folster, Jason P.; Johnson, Paul J. T.; Jackson, Lydgia
- Journal of Bacteriology, Vol. 191, Issue 1
Bile Salts Modulate Expression of the CmeABC Multidrug Efflux Pump in Campylobacter jejuni
journal, October 2005
- Lin, J.; Cagliero, C.; Guo, B.
- Journal of Bacteriology, Vol. 187, Issue 21
Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps
journal, April 2015
- Su, Chih-Chia; Bolla, Jani Reddy; Kumar, Nitin
- Cell Reports, Vol. 11, Issue 1
Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae.
journal, July 1995
- Hagman, K. E.; Shafer, W. M.
- Journal of Bacteriology, Vol. 177, Issue 14
Divergence and transcriptional analysis of the division cell wall (dcw) gene cluster in Neisseria spp.: Neisserial dcw cluster variability
journal, January 2003
- Snyder, Lori A. S.; Shafer, William M.; Saunders, Nigel J.
- Molecular Microbiology, Vol. 47, Issue 2
Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009–2013): coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics
journal, April 2016
- Liang, Jing-Yao; Cao, Wen-Ling; Li, Xiao-Dong
- BMC Infectious Diseases, Vol. 16, Issue 1
The NorM Efflux Pump of Neisseria gonorrhoeae and Neisseria meningitidis Recognizes Antimicrobial Cationic Compounds
journal, February 2003
- Rouquette-Loughlin, Corinne; Dunham, Steven A.; Kuhn, Michael
- Journal of Bacteriology, Vol. 185, Issue 3
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 fitness
journal, October 2008
- Warner, Douglas M.; Shafer, William M.; Jerse, Ann E.
- Molecular Microbiology, Vol. 70, Issue 2
Efflux systems in bacterial pathogens: An opportunity for therapeutic intervention? An industry view
journal, March 2006
- Lynch, A. Simon
- Biochemical Pharmacology, Vol. 71, Issue 7
Effect of efflux pump inhibitors on bile resistance and in vivo colonization of Campylobacter jejuni
journal, September 2006
- Lin, J.; Martinez, A.
- Journal of Antimicrobial Chemotherapy, Vol. 58, Issue 5
Multidrug-Binding Transcription Factor QacR Binds the Bivalent Aromatic Diamidines DB75 and DB359 in Multiple Positions
journal, July 2007
- Brooks, Benjamin E.; Piro, Kevin M.; Brennan, Richard G.
- Journal of the American Chemical Society, Vol. 129, Issue 26
MolProbity : all-atom structure validation for macromolecular crystallography
journal, December 2009
- Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J.
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1
The interaction between bacteria and bile
journal, September 2005
- Begley, Máire; Gahan, Cormac G. M.; Hill, Colin
- FEMS Microbiology Reviews, Vol. 29, Issue 4
Coot model-building tools for molecular graphics
journal, November 2004
- Emsley, Paul; Cowtan, Kevin
- Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132
The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae.
journal, July 1997
- Lucas, C. E.; Balthazar, J. T.; Hagman, K. E.
- Journal of Bacteriology, Vol. 179, Issue 13
Crystal Structure of the Open State of the Neisseria gonorrhoeae MtrE Outer Membrane Channel
journal, June 2014
- Lei, Hsiang-Ting; Chou, Tsung-Han; Su, Chih-Chia
- PLoS ONE, Vol. 9, Issue 6
Discrimination of solvent from protein regions in native Fouriers as a means of evaluating heavy-atom solutions in the MIR and MAD methods
journal, February 1999
- Terwilliger, Thomas C.; Berendzen, Joel
- Acta Crystallographica Section D Biological Crystallography, Vol. 55, Issue 2
Towards an Understanding of Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae: Evidence for a Porin-Efflux Pump Collaboration
journal, April 2006
- Shafer, William M.; Folster, Jason P.
- Journal of Bacteriology, Vol. 188, Issue 7
Fiji: an open-source platform for biological-image analysis
journal, June 2012
- Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
- Nature Methods, Vol. 9, Issue 7
PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
Structure of AmtR, the global nitrogen regulator of Corynebacterium glutamicum , in free and DNA-bound forms
journal, February 2016
- Palanca, Carles; Rubio, Vicente
- FEBS Journal, Vol. 283, Issue 6
The farAB-encoded efflux pump mediates resistance of gonococci to long-chained antibacterial fatty acids
journal, August 1999
- Lee, Eun Hee; Shafer, William M.
- Molecular Microbiology, Vol. 33, Issue 4
Identification of a cell envelope protein (MtrF) involved in hydrophobic antimicrobial resistance in Neisseria gonorrhoeae
journal, November 2002
- Veal, W. L.
- Journal of Antimicrobial Chemotherapy, Vol. 51, Issue 1
Characterization of the MacA–MacB efflux system in Neisseria gonorrhoeae
journal, September 2005
- Rouquette-Loughlin, Corinne E.; Balthazar, Jacqueline T.; Shafer, William M.
- Journal of Antimicrobial Chemotherapy, Vol. 56, Issue 5
Q-SiteFinder: an energy-based method for the prediction of protein-ligand binding sites
journal, February 2005
- Laurie, A. T. R.; Jackson, R. M.
- Bioinformatics, Vol. 21, Issue 9
Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in Patients Recently Treated with Azithromycin
journal, March 2017
- Wind, Carolien M.; de Vries, Esther; Schim van der Loeff, Maarten F.
- Clinical Infectious Diseases, Vol. 65, Issue 1
Regulation of mtrF Expression in Neisseria gonorrhoeae and Its Role in High-Level Antimicrobial Resistance
journal, May 2005
- Folster, J. P.; Shafer, W. M.
- Journal of Bacteriology, Vol. 187, Issue 11
Preparation of selenomethionyl proteins for phase determination
book, January 1997
- Doublié, Sylvie
- Methods in Enzymology
- p. 523-530
Involvement of the gonococcal MtrE protein in the resistance of Neisseria gonorrhoeae to toxic hydrophobic agents
journal, July 1997
- Shafer, W. M.; Delahay, R. M.; Ison, C. A.
- Microbiology, Vol. 143, Issue 7
The crystal structure of the TetR family transcriptional repressor SimR bound to DNA and the role of a flexible N-terminal extension in minor groove binding
journal, August 2011
- Le, Tung B. K.; Schumacher, Maria A.; Lawson, David M.
- Nucleic Acids Research, Vol. 39, Issue 21
FarR Regulates the farAB-Encoded Efflux Pump of Neisseria gonorrhoeae via an MtrR Regulatory Mechanism
journal, December 2003
- Lee, E. -H.; Rouquette-Loughlin, C.; Folster, J. P.
- Journal of Bacteriology, Vol. 185, Issue 24
Salmonella typhimurium acrB -like gene: identification and role in resistance to biliary salts and detergents and in murine infection
journal, January 1996
- Lacroix, Fabrice J. C.; Cloeckaert, Axel; Grépinet, Olivier
- FEMS Microbiology Letters, Vol. 135, Issue 2-3
The integration of macromolecular diffraction data
journal, December 2005
- Leslie, Andrew G. W.
- Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 1
Phaser crystallographic software
journal, July 2007
- McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
- Journal of Applied Crystallography, Vol. 40, Issue 4
Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae
journal, May 2001
- Zarantonelli, L.; Borthagaray, G.; Lee, E. H.
- Journal of Antimicrobial Chemotherapy, Vol. 47, Issue 5
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen
journal, August 2020
- Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe
- JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation
journal, February 2021
- Tillu, Vikas A.; Rae, James; Gao, Ya
- Nature Communications, Vol. 12, Issue 1
Molecular basis for control of antibiotic production by a bacterial hormone
journal, February 2021
- Zhou, Shanshan; Bhukya, Hussain; Malet, Nicolas
- Nature, Vol. 590, Issue 7846
A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition
journal, July 2020
- Sahin, Irem Durmaz; Christodoulou, Michael S.; Guzelcan, Ece Akhan
- Scientific Reports, Vol. 10, Issue 1
Decreased azithromycin susceptibility of Neisseria gonorrhoeae isolates in patients recently treated with azithromycin
journal, March 2017
- Wind, Carolien M.; de Vries, Esther; Schim van der Loeff, Maarten F.
- Clinical Infectious Diseases
Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae
text, January 2002
- A., Nicholas, R.; M., Shafer, W.; L., Veal, W.
- The University of North Carolina at Chapel Hill University Libraries
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
text, January 2010
- Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
- Apollo - University of Cambridge Repository
ImageJ2: ImageJ for the next generation of scientific image data
preprint, January 2017
- Rueden, Curtis T.; Schindelin, Johannes; Hiner, Mark C.
- arXiv
Bacterial antibiotic efflux systems of medical importance
journal, December 1999
- K�hler, T.; Pech�re, J. -C.; Pl�siat, P.
- Cellular and Molecular Life Sciences (CMLS), Vol. 56, Issue 9-10
On the in vivo significance of bacterial resistance to antimicrobial peptides
journal, November 2015
- Bauer, Margaret E.; Shafer, William M.
- Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1848, Issue 11
Characterization of the multidrug efflux regulator AcrR from Escherichia coli
journal, September 2007
- Su, Chih-Chia; Rutherford, Denae J.; Yu, Edward W.
- Biochemical and Biophysical Research Communications, Vol. 361, Issue 1
Efflux systems in bacterial pathogens: An opportunity for therapeutic intervention? An industry view
journal, March 2006
- Lynch, A. Simon
- Biochemical Pharmacology, Vol. 71, Issue 7
The interaction between bacteria and bile
journal, September 2005
- Begley, Máire; Gahan, Cormac G. M.; Hill, Colin
- FEMS Microbiology Reviews, Vol. 29, Issue 4
Crystal Structures of Multidrug Binding Protein TtgR in Complex with Antibiotics and Plant Antimicrobials
journal, June 2007
- Alguel, Yilmaz; Meng, Cuixiang; Terán, Wilson
- Journal of Molecular Biology, Vol. 369, Issue 3
Bile salts enhance bacterial co-aggregation, bacterial-intestinal epithelial cell adhesion, biofilm formation and antimicrobial resistance of Bacteroides fragilis
journal, August 2007
- Pumbwe, Lilian; Skilbeck, Christopher A.; Nakano, Viviane
- Microbial Pathogenesis, Vol. 43, Issue 2-3
Multidrug-Binding Transcription Factor QacR Binds the Bivalent Aromatic Diamidines DB75 and DB359 in Multiple Positions
journal, July 2007
- Brooks, Benjamin E.; Piro, Kevin M.; Brennan, Richard G.
- Journal of the American Chemical Society, Vol. 129, Issue 26
A comprehensive fluorescent sensor for spatiotemporal cell cycle analysis in Arabidopsis
journal, September 2020
- Desvoyes, Bénédicte; Arana-Echarri, Ainhoa; Barea, María D.
- Nature Plants, Vol. 6, Issue 11
Multidrug efflux pumps: structure, function and regulation
journal, July 2018
- Du, Dijun; Wang-Kan, Xuan; Neuberger, Arthur
- Nature Reviews Microbiology, Vol. 16, Issue 9
Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines
journal, April 2007
- Workowski, K. A.; Berman, S. M.
- Clinical Infectious Diseases, Vol. 44, Issue Supplement 3
Decreased Azithromycin Susceptibility of Neisseria gonorrhoeae Isolates in Patients Recently Treated with Azithromycin
journal, March 2017
- Wind, Carolien M.; de Vries, Esther; Schim van der Loeff, Maarten F.
- Clinical Infectious Diseases, Vol. 65, Issue 1
Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae
journal, May 2001
- Zarantonelli, L.; Borthagaray, G.; Lee, E. H.
- Journal of Antimicrobial Chemotherapy, Vol. 47, Issue 5
Identification of a cell envelope protein (MtrF) involved in hydrophobic antimicrobial resistance in Neisseria gonorrhoeae
journal, November 2002
- Veal, W. L.
- Journal of Antimicrobial Chemotherapy, Vol. 51, Issue 1
Characterization of the MacA–MacB efflux system in Neisseria gonorrhoeae
journal, September 2005
- Rouquette-Loughlin, Corinne E.; Balthazar, Jacqueline T.; Shafer, William M.
- Journal of Antimicrobial Chemotherapy, Vol. 56, Issue 5
The crystal structure of the TetR family transcriptional repressor SimR bound to DNA and the role of a flexible N-terminal extension in minor groove binding
journal, August 2011
- Le, Tung B. K.; Schumacher, Maria A.; Lawson, David M.
- Nucleic Acids Research, Vol. 39, Issue 21
The MtrD protein of Neisseria gonorrhoeae is a member of the resistance/nodulation/division protein family constituting part of an efflux system
journal, July 1997
- Nilles, Matthew; Lucas, Claressa E.; Balthazar, Jacqueline T.
- Microbiology, Vol. 143, Issue 7
Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae
journal, March 1998
- Veal, W. L.; Yellen, A.; Balthazar, J. T.
- Microbiology, Vol. 144, Issue 3
Structure of AmtR, the global nitrogen regulator of Corynebacterium glutamicum , in free and DNA-bound forms
journal, February 2016
- Palanca, Carles; Rubio, Vicente
- FEBS Journal, Vol. 283, Issue 6
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 fitness
journal, October 2008
- Warner, Douglas M.; Shafer, William M.; Jerse, Ann E.
- Molecular Microbiology, Vol. 70, Issue 2
Salmonella typhimurium acrB -like gene: identification and role in resistance to biliary salts and detergents and in murine infection
journal, January 1996
- Lacroix, Fabrice J. C.; Cloeckaert, Axel; Grépinet, Olivier
- FEMS Microbiology Letters, Vol. 135, Issue 2-3
Structural Mechanisms of QacR Induction and Multidrug Recognition
journal, December 2001
- Schumacher, M. A.
- Science, Vol. 294, Issue 5549
Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae.
journal, July 1995
- Hagman, K. E.; Shafer, W. M.
- Journal of Bacteriology, Vol. 177, Issue 14
The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae.
journal, July 1997
- Lucas, C. E.; Balthazar, J. T.; Hagman, K. E.
- Journal of Bacteriology, Vol. 179, Issue 13
Overexpression of the MtrC-MtrD-MtrE Efflux Pump Due to an mtrR Mutation Is Required for Chromosomally Mediated Penicillin Resistance in Neisseria gonorrhoeae
journal, October 2002
- Veal, W. L.; Nicholas, R. A.; Shafer, W. M.
- Journal of Bacteriology, Vol. 184, Issue 20
Characterization of the Multiple Transferable Resistance Repressor, MtrR, from Neisseria gonorrhoeae
journal, July 2005
- Hoffmann, Katherine M.; Williams, Daniel; Shafer, William M.
- Journal of Bacteriology, Vol. 187, Issue 14
The TetR Family of Transcriptional Repressors
journal, June 2005
- Ramos, J. L.; Martinez-Bueno, M.; Molina-Henares, A. J.
- Microbiology and Molecular Biology Reviews, Vol. 69, Issue 2
Azithromycin-resistant Neisseria gonorrhoeae isolates in Guangzhou, China (2009–2013): coevolution with decreased susceptibilities to ceftriaxone and genetic characteristics
journal, April 2016
- Liang, Jing-Yao; Cao, Wen-Ling; Li, Xiao-Dong
- BMC Infectious Diseases, Vol. 16, Issue 1
Crystal Structure of the Open State of the Neisseria gonorrhoeae MtrE Outer Membrane Channel
journal, June 2014
- Lei, Hsiang-Ting; Chou, Tsung-Han; Su, Chih-Chia
- PLoS ONE, Vol. 9, Issue 6
Crystal Structure of the Neisseria gonorrhoeae MtrD Inner Membrane Multidrug Efflux Pump
journal, June 2014
- Bolla, Jani Reddy; Su, Chih-Chia; Do, Sylvia V.
- PLoS ONE, Vol. 9, Issue 6
Modification of a PCRBased Site-Directed Mutagenesis Method
journal, October 1997
- Fisher, Constance L.; Pei, Guo Kui
- BioTechniques, Vol. 23, Issue 4