Multidrug efflux pumps have emerged as relevant elements in the intrinsic and acquired antibiotic resistance of bacterial pathogens. In contrast with other antibiotic resistance genes that have been obtained by virulent bacteria through horizontal gene transfer, genes coding for multidrug efflux pumps are present in the chromosomes of all living organisms. In addition, these genes are highly conserved (all members of the same species contain the same efflux pumps) and their expression is tightly regulated. Together, these characteristics suggest that the main function of these systems is not resisting the antibiotics used in therapy and that they should have other roles relevant to the behavior of bacteria in their natural ecosystems. Among the potential roles, it has been demonstrated that efflux pumps are important for processes of detoxification of intracellular metabolites, bacterial virulence in both animal and plant hosts, cell homeostasis and intercellular signal trafficking.

SummaryPseudomonas aeruginosa in the lungs of cystic fibrosis patients grows to high densities in mucopurulent material that is depleted in oxygen. Some have concluded that growth in these circumstances is dependent on anaerobic nitrate respiration. Here we present data in favour of the alternative hypothesis that microaerobic respiration is the predominant mode of P. aeruginosa growth in the cystic fibrosis lung. We found that P. aeruginosa strain PAO1 and a mucoid derivative of strain PAO1 each grew at dissolved oxygen concentrations of less than 3 mM. This is lower than the concentration of oxygen that has been measured in hypoxic cystic fibrosis mucous. A transcriptome analysis comparing cells grown under aerobic conditions (185 mM dissolved oxygen) with cells grown with 20 mM or 3 mM dissolved oxygen, or anaerobically with nitrate, revealed that overlapping sets of genes are expressed depending on oxygen availability. This suggests that P. aeruginosa responds to changes in oxygen concentration along a continuum rather than having a discrete low oxygen regulon. Any one of three high affinity terminal oxidases that P. aeruginosa encodes supported microaerobic growth. A triple mutant lacking all three of these oxidases failed to grow at low oxygen and formed abnormal biofilms.

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