1887

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.

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/content/journal/micro/10.1099/mic.0.000787
2019-05-01
2019-10-14
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