Abstract
BackgroundThe ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa. It was demonstrated that in the presence of antimicrobials, ParR enhances bacterial survival by distinct mechanisms including activation of the mexXY efflux genes, enhancement of lipopolysaccharide modification through the arn operon, and reduction of the expression of oprD porin.ResultsIn this study, we report on transcriptomic analyses of P. aeruginosa PAO1 wild type and parS and parR mutants growing in a defined minimal medium. Our transcriptomic analysis provides the first estimates of transcript abundance for the 5570 coding genes in P. aeruginosa PAO1. Comparative transcriptomics of P. aeruginosa PAO1 and par mutants identified a total of 464 genes regulated by ParS and ParR. Results also showed that mutations in the parS/parR system abolished expression of the mexEF-oprN operon by down-regulating the regulatory gene mexS. In addition to the known effects on drug resistance genes, transcript abundances of the quorum sensing genes (rhlIR and pqsABCDE-phnAB) were higher in both parS and parR mutants. In accordance with these results, a significant portion of the ParS/ParR regulated genes belonged to the MexEF-OprN and quorum sensing regulons. Deletion of the par genes also led to increased phenazine production and swarming motility, consistent with the up-regulation of the phenazine and rhamnolipid biosynthetic genes, respectively.ConclusionOur results link the ParS/ParR two component signal transduction system to MexEF-OprN and quorum sensing systems in P. aeruginosa. These results expand our understanding of the roles of the ParS/ParR system in the regulation of gene expression in P. aeruginosa, especially in the absence of antimicrobials.
Highlights
The ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa
The quantitative reverse transcriptase polymerase chain reaction (qRT-Polymerase chain reaction (PCR)) results showed that the transcript abundance of parS and parR was 3–6 fold higher when grown in AB minimal medium + 2% casamino acids (CAA) as compared to LB medium
The major components of the ParS/ParR signal transduction pathway in P. aeruginosa PAO1 were identified in bacteria grown without antimicrobials (Figure 6)
Summary
The ParS/ParR two component regulatory system plays critical roles for multidrug resistance in Pseudomonas aeruginosa. Pseudomonas aeruginosa is a Gram-negative, metabolically versatile and environmentally ubiquitous bacterial species that is capable of surviving in a variety of animal and plant hosts and causing opportunistic infections in humans. It is responsible for serious chronic and often fatal lung infections in patients with cystic fibrosis and acute infections in patients that are immune adaption occurs largely as a result of expression of the mexXY-oprM efflux [7] and arnBCADTEF-ugd lipopolysaccharide modification operons [8,9]. Among them are genes encoding the outer membrane porin protein OprD, the RND efflux pump MexXY-OprM, and the arnBCADTEF-ugd lipopolysaccharide modification operon
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