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The transcriptional repressor SmvR is important for chlorhexidine decreased susceptibility in Enterobacter cloacae complex

Abstract : Major Facilitator Superfamily (MFS) efflux pumps have been shown to be important for bacterial cells to cope with biocides such as chlorhexidine (CHX), a widely used molecule in hospital settings. In this work, we evaluated the role of two genes smvA and smvR in CHX resistance in Enterobacter cloacae complex (ECC). smvA encodes an MFS pump whereas smvR, located upstream of smvA, codes for a TetR-type transcriptional repressor. To this aim, we constructed corresponding deletion mutants from the ATCC 13047 strain (MIC = 2 mg/L) as well as strains overexpressing smvA or smvR both in ATCC 13047 and three clinical isolates exhibiting elevated MICs of CHX (16-32 mg/L). Determination of MICs revealed that smvA played a modest role in CHX resistance, contrarily to smvR that modulated the ability of ECC to survive in the presence of CHX. In clinical isolates, the overexpression of smvR significantly reduced MICs of CHX (2-8 mg/L). Sequences analyses of smvR and promotor regions pointed out substitutions in conserved regions. Moreover, transcriptional studies revealed that SmvR acted as a repressor of smvA expression even if no quantitative correlation between the level of smvA mRNA and MICs of CHX could be observed. On the other hand, overproduction of smvA was able to complement the lack of the major resistance-nodulation-cell division (RND) superfamily efflux pump AcrB and restored resistance to ethidium bromide and acriflavine. Although SmvA could efflux biocides such as CHX, other actors, of which the expression is under SmvR control, should play critical role in ECC.
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Submitted on : Wednesday, December 11, 2019 - 3:32:22 PM
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François Guérin, François Gravey, Patrick Plesiat, Marion Aubourg, Racha Beyrouthy, et al.. The transcriptional repressor SmvR is important for chlorhexidine decreased susceptibility in Enterobacter cloacae complex. Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2019, 64 (1), pp.e01845-19. ⟨10.1128/AAC.01845-19⟩. ⟨hal-02397671⟩

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