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Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae

Year: 2019
Type: article
Abstract: Neisseria gonorrhoeae causes 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 of mtrCDE expression after exposure to intrinsic and clinically applied antimicrobials.
DOI: 10.1128/jb.00401-19
Authors: Grace A. Beggs, Yaramah M. Zalucki, Nicholas Gene Brown, Sheila Rastegari, Rebecca K. Phillips, Timothy Palzkill, William M. Shafer, Muthiah Kumaraswami, Richard G. Brennan
Institutions: Duke University, Duke Medical Center, Emory University, Baylor College of Medicine, Houston Methodist, The University of Texas MD Anderson Cancer Center, Houston Methodist Research Institute, Veterans Health Administration, Atlanta VA Medical Center
Language: English
Open Access status: hybrid
OpenAlex ID: W2963585748
FWCI: 0.759
Cites: 67
Cited by: 16
Related to: 10