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MBio. 2016 Apr 19;7(2):e00430-16. doi: 10.1128/mBio.00430-16.

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

Author information

  • 1Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
  • 2Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
  • 3Public Health England, Microbiology Services Division, Porton Down, Salisbury, United Kingdom.
  • 4Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
  • 5Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • 6Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom l.j.v.piddock@bham.ac.uk.

Abstract

The opportunistic pathogen Acinetobacter baumannii is 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 an ex vivo porcine 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. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes 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 baumannii is 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 the A. baumannii efflux 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 by A. baumannii and provides a good target for drug discovery.

PMID:
27094331
PMCID:
PMC4850262
DOI:
10.1128/mBio.00430-16
[PubMed - indexed for MEDLINE]
Free PMC Article
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