The Acinetobacter baumannii Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner.
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 [corrected].
Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Grace E
GE
Richmond
Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Laura P
LP
Evans
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Michele J
MJ
Anderson
Public Health England, Microbiology Services Division, Porton Down, Salisbury, United Kingdom.
Matthew E
ME
Wand
Public Health England, Microbiology Services Division, Porton Down, Salisbury, United Kingdom.
Laura C
LC
Bonney
Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom.
Alasdair
A
Ivens
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Kim Lee
KL
Chua
Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Mark A
MA
Webber
Public Health England, Microbiology Services Division, Porton Down, Salisbury, United Kingdom.
J Mark
JM
Sutton
Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Marnie L
ML
Peterson
Antimicrobial Agents Research Group, Institute of Microbiology and Infection, University of Birmingham, Edgbaston, Birmingham, United Kingdom l.j.v.piddock@bham.ac.uk.
Laura J V
LJ
Piddock
D000151:Acinetobacter Infections / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018441:Biofilms; D024901:Drug Resistance, Multiple, Bacterial; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014774:Virulence
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins