1887

Abstract

is a Gram-negative bacillus that causes serious infections in immunocompromised human hosts and exhibits significant multidrug resistance. In this study, we identified a novel -family regulator (designated ) in the genome of NTUH-K2044 whose functions have remained enigmatic so far. Functional characterization of the putative regulator with respect to cellular physiology and antimicrobial susceptibility was performed by generating an isogenic mutant, Δ in a hypervirulent clinical isolate of . The mutant was sensitive to hyperosmotic and bile conditions. Disruption of increased the susceptibility of to oxidative (0.78947 mM hydrogen peroxide) and nitrosative (30 mM acidified nitrite) stress by ~1.4-fold and ~10-fold, respectively. Loss of the regulator led to a decrease in the minimum inhibitory concentrations for chloramphenicol (10-fold), erythromycin (6-fold), nalidixic acid (>50-fold) and trimethoprim (10-fold), which could be restored following complementation. The relative change in expression of resistance–nodulation–cell division super family (RND) efflux gene was decreased by approximately fivefold in the mutant as evidenced by qRT-PCR. In a model, the mutant exhibited significantly (<0.01) lower virulence. Overall, results detailed in this report reflect the pleiotropic role of the signalling system and diversity of the resistance determinants in hypervirulent K1 serotype NTUH-K2044.

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2013-07-01
2019-12-06
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