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Volume 170, Issue 2

P-type ATPase zinc transporter Rv3270 of enhances multi-drug efflux activity Open Access

Graphical Abstract

: The probable model depicting antibiotic export by Rv3270

(a) Antibiotics are reported to enter the cells through porin channels such as Msp family porins .(b) Zn (green dots) imported into the cells through probable Zn importers such as ZIP transporters. (c) Zinc inside the cells may influence the efflux of antibiotics by a co-transportation process through Rv3270 triggered by ATP hydrolysis. (d) Rv3270 possibly captures beta-lactams and extrudes them out of the cells via hypothetical linking proteins (outer membrane efflux adaptor proteins) and porins (Msp family) like AcrAB-TolC and Rv0194. This maintains a lower concentration of the antibiotic inside the cell, reducing its chances of exerting inhibitory effects on cell wall synthesis.

Abstract

Metal homeostasis is maintained by the uptake, storage and efflux of metal ions that are necessary for the survival of the bacterium. Homeostasis is mostly regulated by a group of transporters categorized as ABC transporters and P-type ATPases. On the other hand, efflux pumps often play a role in drug–metal cross-resistance. Here, with the help of antibiotic sensitivity, antibiotic/dye accumulation and semi-quantitative biofilm formation assessments we report the ability of Rv3270, a P-type ATPase known for its role in combating Mn and Zn metal ion toxicity in , in influencing the extrusion of multiple structurally unrelated drugs and enhancing the biofilm formation of and Overexpression of Rv3270 increased the tolerance of host cells to norfloxacin, ofloxacin, sparfloxacin, ampicillin, oxacillin, amikacin and isoniazid. A significantly lower accumulation of norfloxacin, ethidium bromide, bocillin FL and levofloxacin in cells harbouring Rv3270 as compared to host cells indicated its role in enhancing efflux activity. Although over-expression of Rv3270 did not alter the susceptibility levels of levofloxacin, rifampicin and apramycin, the presence of a sub-inhibitory concentration of Zn resulted in low-level tolerance towards these drugs. Of note, the expression of Rv3270 enhanced the biofilm-forming ability of the host cells strengthening its role in antimicrobial resistance. Therefore, the study indicated that the over-expression of Rv3270 enhances the drug efflux activity of the micro-organism where zinc might facilitate drug–metal cross-resistance for some antibiotics.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): biofilm , efflux pump inhibitors , efflux pumps , metal transporter , metal–antibiotic cross resistance and Mycobacterium tuberculosis
Funding
This study was supported by the:
  • Albert David Limited (Award TN: AP: 204)
    • Principle Award Recipient: AnindyaS Ghosh
  • Department of Biotechnology, Ministry of Science and Technology, India (Award BT/PR40383/BCE/8/1561/2020)
    • Principle Award Recipient: AnindyaS Ghosh
© 2024 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2024-02-19
2025-03-21
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P-type ATPase zinc transporter Rv3270 of Mycobacterium tuberculosis enhances multi-drug efflux activity
Microbiology 170, 001441 (2024); https://doi.org/10.1099/mic.0.001441
/content/journal/micro/10.1099/mic.0.001441
/content/journal/micro/10.1099/mic.0.001441
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