title: An ace up their sleeve: a transcriptomic approach exposes the AceI eﬄux protein of Acinetobacter baumannii and reveals the drug eﬄux potential hidden in many microbial pathogens.
abstract: The era of antibiotics as a cure-all for bacterial infections appears to be coming to an end. The emergence of multidrug resistance in many hospital-associated pathogens has resulted in "superbugs" that are effectively untreatable. Multidrug eﬄux pumps are well known mediators of bacterial drug resistance. Genome sequencing efforts have highlighted an abundance of putative eﬄux pump genes in bacteria. However, it is not clear how many of these pumps play a role in antimicrobial resistance. Eﬄux pump genes that participate in drug resistance can be under tight regulatory control and expressed only in response to substrates. Consequently, changes in gene expression following antimicrobial shock may be used to identify eﬄux pumps that mediate antimicrobial resistance. Using this approach we have characterized several novel eﬄux pumps in bacteria. In one example we recently identified the Acinetobacterchlorhexidine eﬄux protein (AceI) eﬄux pump in Acinetobacter. AceI is a prototype for a novel family of multidrug eﬄux pumps conserved in many proteobacterial lineages. The discovery of this family raises the possibility that additional undiscovered intrinsic resistance proteins may be encoded in the core genomes of pathogenic bacteria.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Hassan
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Liam D H
authors.initials: LD
authors.lastname: Elbourne
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Hasinika K A H
authors.initials: HK
authors.lastname: Gamage
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds Leeds, UK.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Jackson
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds Leeds, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sharples
authors.affiliation: Laboratory for Microbial Dynamics, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo Oslo, Norway.
authors.forename: Anne-Brit
authors.initials: AB
authors.lastname: Kolstø
authors.affiliation: Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, University of Leeds Leeds, UK.
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Henderson
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University Sydney, NSW, Australia.
authors.forename: Ian T
authors.initials: IT
authors.lastname: Paulsen
keywords: adaptive resistance; bacterial drug resistance transcriptomics; bacterial transmembrane pair; multidrug eﬄux systems