1887

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Volume 165, Issue 5

The aminoglycoside resistance-promoting AmgRS envelope stress-responsive two-component system in is zinc-activated and protects cells from zinc-promoted membrane damage Free

Abstract

Exposure of wild-type (WT) PAO1 to ZnCl (Zn) yielded a concentration-dependent increase in depolarization of the cytoplasmic membrane (CM), an indication that this metal is membrane-damaging. Consistent with this, Zn activated the AmgRS envelope stress-responsive two-component system (TCS) that was previously shown to be activated by and to protect from the membrane-damaging effects of aminoglycoside (AG) antibiotics. A mutant lacking showed enhanced Zn-promoted CM perturbation and was Zn-sensitive, an indication that the TCS protected cells from the CM-damaging effects of this metal. In agreement with this, a mutant carrying an AmgRS-activating mutation was less susceptible to Zn-promoted CM perturbation and more tolerant of elevated levels of Zn than WT. AG activation of AmgRS is known to drive expression of the AG resistance-promoting multidrug efflux operon, and while Zn similarly induced expression this was independent of AmgRS and reliant on a second TCS implicated in regulation, ParRS. MexXY did not, however, contribute to Zn resistance or protection from Zn-promoted CM damage. Despite its activation of AmgRS and induction of , Zn had a minimal impact on the AG resistance of WT although, given that Zn-tolerant AmgRS-activated mutant strains are AG resistant, there is still the prospect of this metal promoting AG resistance development in this organism.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): aminoglycoside , envelope stress , Pseudomonas aeruginosa , two-component system and zinc
© 2019 The Authors
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2019-05-01
2023-12-07
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The aminoglycoside resistance-promoting AmgRS envelope stress-responsive two-component system in Pseudomonas aeruginosa is zinc-activated and protects cells from zinc-promoted membrane damage
Microbiology 165, 563 (2019); https://doi.org/10.1099/mic.0.000787
/content/journal/micro/10.1099/mic.0.000787
/content/journal/micro/10.1099/mic.0.000787
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