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 Acinetobacter chlorhexidine 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.

Highlights

  • Multidrug efflux pumps are a significant obstacle preventing the control of infections caused by pathogenic bacteria

  • Given that the Proteobacterial Antimicrobial Compound Efflux (PACE) family represents a new class of resistance determinants, we were interested in gathering basic information regarding the mode of inheritance of these genes in bacteria

  • We examined PACE family protein conservation in four γ-Proteobacterial species (A. baumannii, P. aeruginosa, V. parahaemolyticus, and E. coli) a β-Proteobacterial species (B. cenocepacia) and a member of the Firmicutes (Veillonella parvula)

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Summary

Introduction

Multidrug efflux pumps are a significant obstacle preventing the control of infections caused by pathogenic bacteria. Genes encoding these transporters have been found in all bacterial genomes sequenced, and the overexpression of just one can lead to the reduced efficacy of a range of structurally and mechanistically unrelated antimicrobials (Ren and Paulsen, 2007; Brzoska et al, 2013). Bacterial drug resistance can be divided into three general categories, intrinsic, adaptive, and acquired (Fernandez and Hancock, 2012) Depending on their mode(s) of regulation and their local genetic context, bacterial multidrug efflux pumps can be geared to participate in any of these three resistance categories. Acquired resistance can result from mutations promoting constitutive expression of an ordinarily tightly controlled endogenous multidrug efflux system, or when efflux pump genes are acquired on a mobile genetic element, such as a plasmid or phage

Adaptive Resistance Responses Identify Efflux Pumps that Mediate Drug Resistance
Adaptive Resistance Responses Identify a New Class of Drug Efflux Pump
PACE Family Proteins are Encoded Within the Core Genome
Physiological Substrates for PACE Family Transporters
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