- Inactivation of MuxABC-OpmB Transporter System in Pseudomonas aeruginosa Leads to Increased Ampicillin and Carbenicillin Resistance and Decreased Virulence
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Liang Yang , Lin Chen , Lixin Shen , Michael Surette , Kangmin Duan
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J. Microbiol. 2011;49(1):107-114. Published online March 3, 2011
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DOI: https://doi.org/10.1007/s12275-011-0186-2
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Resistance-Nodulation-Cell Division (RND) pumps play important roles in bacterial resistance to antibiotics. Pseudomonas aeruginosa is an important human pathogen which exhibits high level resistance to antibiotics. There are total of 12 RND pumps present in the P. aeruginosa PAO1 genome. The recently characterized MuxABC-OpmB system has been shown to play a role in resistance to novobiocin, aztreonam, macrolides, and tetracycline in a multiple knockout mutation. In this study, we examined the expression levels of all the 12 RND pump gene clusters and tested the involvement of MuxABC-OpmB in pathogenicity. The results indicated that in addition to the four known constitutively expressed RND pumps, mexAB-oprM, mexGHIopmD, mexVW, and mexXY, relatively high levels of expression were observed with mexJK and muxABCopmB in the conditions tested. Inactivation of muxA in the muxABC-opmB operon resulted in elevated resistance to ampicillin and carbenicillin. The mutant also showed attenuated virulence in both Brassica rapa
pekinensis and Drosophila melanogaster infection models. The decreased virulence at least in part was due to decreased twitching motility in the mutant. These results indicate that the RND pump MuxABC-OpmB is associated with ampicillin and carbenicillin susceptibility and also involved in pathogenesis in P. aeruginosa.
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- Modulation of Secreted Virulence Factor Genes by Subinhibitory Concentrations of Antibiotics in Pseudomonas aeruginosa
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Lixin Shen , Ying Shi , Dan Zhang , Jinhua Wei , Michael G. Surette , Kangmin Duan
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J. Microbiol. 2008;46(4):441-447. Published online August 31, 2008
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DOI: https://doi.org/10.1007/s12275-008-0054-x
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Recent studies have shown that subinhibitory antibiotics play important roles in regulating bacterial genes including virulence factor genes. In this study, the expression of 13 secreted virulence related gene clusters of Pseudomonas aeruginosa, an important opportunistic pathogen, was examined in the presence of subinhibitory concentrations of 4 antibiotics: vancomycin, tetracycline, ampicilin and azithromycin. Activation of gene expression was observed with phzA1, rhlAB, phzA2, lasB, exoY, and exoS. Subinhibitory concentrations of vancomycin resulted in more than 10-fold increase of rhlAB and phzA2 transcription. Both rhamnolipid production and pyocyanin production were significantly elevated, correlating phenotypes with the increased transcription. P. aeruginosa swarming and swimming motility also increased. Similar results were observed with subinhibitory tetracycline, azithromycin and ampicillin. These results indicate that the antibiotics at low concentrations can up-regulate virulence factors and therefore influence bacterial
pathogenesis.
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