Mary K. Phillips-Jones
Antimicrobial resistance (AMR) nanomachines—mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation
Phillips-Jones, Mary K.; Harding, Stephen E.
Abstract
In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments.
Citation
Phillips-Jones, M. K., & Harding, S. E. (2018). Antimicrobial resistance (AMR) nanomachines—mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation. Biophysical Reviews, 10(2), 347-362. https://doi.org/10.1007/s12551-018-0404-9
Journal Article Type | Article |
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Acceptance Date | Feb 4, 2018 |
Online Publication Date | Mar 10, 2018 |
Publication Date | 2018-04 |
Deposit Date | Feb 15, 2018 |
Publicly Available Date | Mar 10, 2018 |
Journal | Biophysical Reviews |
Print ISSN | 1867-2450 |
Electronic ISSN | 1867-2469 |
Publisher | Springer Verlag |
Peer Reviewed | Peer Reviewed |
Volume | 10 |
Issue | 2 |
Pages | 347-362 |
DOI | https://doi.org/10.1007/s12551-018-0404-9 |
Keywords | Antimicrobial Resistance; Glycopeptide; Fluoroquinolone; Hydrodynamics; Analytical Ultracentrifugation; Circular dichroism spectroscopy |
Public URL | https://nottingham-repository.worktribe.com/output/962239 |
Publisher URL | https://link.springer.com/article/10.1007%2Fs12551-018-0404-9 |
Contract Date | Feb 15, 2018 |
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