The Acinetobacter baumannii Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner

Grace E Richmond, Laura P Evans, Michele J Anderson, Matthew E Wand, Laura C Bonney, Alasdair Ivens, Kim Lee Chua, Mark A Webber, J Mark Sutton, Marnie L Peterson, Laura J V Piddock

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)
117 Downloads (Pure)

Abstract

The opportunistic pathogen Acinetobacter baumanniiis able to persist in the environment and is often multidrug resistant (MDR), causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in anex vivoporcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example,A. baumanniilacking AdeRS displayed decreased expression of adeABC,pilgenes,comgenes, and apgaC-like gene, whereas loss of AdeB resulted in increased expression of pilandcomgenes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery.

IMPORTANCE: Acinetobacter baumanniiis a nosocomial pathogen and is an increasing problem in hospitals worldwide. This organism is often multidrug resistant, can persist in the environment, and forms a biofilm on environmental surfaces and wounds. Overproduction of efflux pumps can allow specific toxic compounds to be pumped out of the cell and can lead to multidrug resistance. This study demonstrates the role of theA. baumanniiefflux pump AdeB, and its regulator AdeRS, in multidrug resistance, epithelial cell killing, and biofilm formation. Deletion of the genes encoding these systems led to increased susceptibility to antibiotics, decreased biofilm formation on biotic and abiotic surfaces, and decreased virulence. Our data suggest that inhibition of AdeB could prevent biofilm formation or colonization in patients byA. baumanniiand provides a good target for drug discovery.

Original languageEnglish
Article numbere00430-16
JournalmBio
Volume7
Issue number2
DOIs
Publication statusPublished - 19 Apr 2016

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