The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
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
Abstract
Summary: The MtrC‐MtrD‐MtrE efflux pump system confers resistance to macrolide antibiotics and antimicrobial substances of the host innate defence. Clinical isolates with increased resistance to erythromycin and azithromycin frequently harbour mutations in the mtrR structural gene, which encodes a repressor of the mtrCDE operon, or the mtrR promoter region. The MtrC‐MtrD‐MtrE system is important for gonococcal survival in the murine genital tract, and derepression of the mtrCDE operon via deletion of mtrR confers increased fitness in vivo. Here we compared isogenic strains with naturally occurring mtrR locus mutations for differences in mtrCDE expression and pump‐related phenotypes. Mutations upstream of mtrC, including those within the MtrR binding region and a novel mutation that increases mtrC RNA stability conferred the highest levels of derepression as measured by mtrCDE transcription and resistance to antibiotics, progesterone and antimicrobial peptides. In contrast, mutations within the mtrR coding sequence conferred low to intermediate levels of derepression. In vivo, the mtr mutants were more fit than the wild‐type strain, the degree to which paralleled in vitro resistance gradients. 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.
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“Clinically relevant mutations that result in the overexpression of the MtrCDE efflux pump generally result in increased resistance to hydrophobic agents and, correspondingly, increased bacterial burden in vaginal lavage fluids of infected mice (124).”
From Overcoming the Heme Paradox: Heme Toxicity and Tolerance in Bacterial Pathogens (2010) · cites this paper as [124]
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Cites
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Self-citationNishino, K., Latifi, T., & Groisman, E. A. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04940.x · Cited by 385
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Cited by
Molecular mechanisms of antibiotic resistance
Blair, J. M. A., Webber, M. A., Baylay, A. J., Ogbolu, D. O., & Piddock, L. J. V. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3380 · Cited by 4,092
Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance.
Blair, J. M., Richmond, G. E., & Piddock, L. J. (2014) · Future Microbiology · doi:10.2217/fmb.14.66 · Cited by 481
Overcoming the Heme Paradox: Heme Toxicity and Tolerance in Bacterial Pathogens
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Deep sequencing-based analysis of the anaerobic stimulon in Neisseria gonorrhoeae
Isabella, V. M., & Clark, V. L. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-51 · Cited by 84
Lewis, L. A., Gulati, S., Burrowes, E., Zheng, B., Ram, S., & Rice, P. A. (2015) · mBio · doi:10.1128/mbio.02465-14 · Cited by 43
Metadata
- Authors
- Warner, D. M., Shafer, W. M., & Jerse, A. E.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2008-09-25
- Volume
- 70
- Issue
- 2
- Pages
- 462-478
- ISSN
- 0950-382X
- 1365-2958
- PMC
- PMC2602950
- Cited by
- 192
- References
- 68
- Language
- en
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- Warner, D. M., Shafer, W. M., & Jerse, A. E. (2008). 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. Molecular Microbiology. https://doi.org/10.1111/j.1365-2958.2008.06424.x
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