Abstract
Pseudomonas aeruginosa is a key opportunistic pathogen characterized by its biofilm formation ability and high-level multiple antibiotic resistance. By screening a library of random transposon insertion mutants with an increased biofilm-specifc antibiotic susceptibility, we previously identified 3 genes or operons of P. aeruginosa UCBPP-PA14 (ndvB, PA1875–1877 and tssC1) that do not affect biofilm formation but are involved in biofilm-specific antibiotic resistance. In this study, we demonstrate that PA0756–0757 (encoding a putative two-component regulatory system), PA2070 and PA5033 (encoding hypothetical proteins of unknown function) display increased expression in biofilm cells and also have a role in biofilm-specific antibiotic resistance. Furthermore, deletion of each of PA0756, PA2070 and PA5033 resulted in a significant reduction of lethality in Caenorhabditis elegans, indicating a role for these genes in both biofilm-specific antibiotic resistance and persistence in vivo. Together, these data suggest that these genes are potential targets for antimicrobial agents.
Highlights
Pseudomonas aeruginosa is a well-established opportunistic pathogen capable of infecting animals and plants as demonstrated with strain UCBPP-PA14 (PA14) [1]
PA1875–1877 is part of an operon that encodes an efflux pump that removes antibiotics from the cells within the biofilm [11]. tssC1 is a component of a P. aeruginosa type VI secretion system that is involved in biofilm-specific antibiotic resistance through an unknown mechanism [12]
We have described the identification of three novel biofilm-specific antibiotic resistance genes in P. aeruginosa
Summary
Pseudomonas aeruginosa is a well-established opportunistic pathogen capable of infecting animals and plants as demonstrated with strain UCBPP-PA14 (PA14) [1]. Analysis of deletion mutants of these genes revealed that these mutants share a common phenotype: they form biofilms and grow as well as the wild type strain, yet they display a significant decrease in biofilm-specific resistance relative to the wild type strain [10,11,12]. These mutants have no defect in planktonic antibiotic resistance. PA1875–1877 is part of an operon that encodes an efflux pump that removes antibiotics from the cells within the biofilm [11]. tssC1 is a component of a P. aeruginosa type VI secretion system that is involved in biofilm-specific antibiotic resistance through an unknown mechanism [12]
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