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Ribosome protection prevents azithromycin-mediated quorum-sensing modulation and stationary-phase killing of Pseudomonas aeruginosa

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Published in Antimicrobial Agents and Chemotherapy. 2007, vol. 51, no. 12, p. 4243-4248
Abstract In Pseudomonas aeruginosa, azithromycin has been shown to reduce virulence factor production, to retard biofilm formation, and to exhibit bactericidal effects on stationary-phase cells. In this study we analyzed whether these azithromycin-mediated effects require interaction with the ribosome. We blocked the access of azithromycin to the ribosome in P. aeruginosa PAO1 by expressing the 23S rRNA methylase ErmBP from Clostridium perfringens. Ribosome protection prevented the azithromycin-mediated reduction of elastase and rhamnolipid production, as well as the inhibition of swarming motility. Ribosome protection also prevented the killing of stationary-phase cells, suggesting that the cell-killing effect of azithromycin does not result solely from membrane destabilization. We further show that rhamnolipids are involved in cell killing, probably by increasing the uptake of the hydrophobic azithromycin molecule. These results have important implications for the treatment with azithromycin of patients chronically colonized by P. aeruginosa and might explain the variability in the efficacy of azithromycin treatments.
Keywords Anti-Bacterial Agents/pharmacologyAzithromycin/ pharmacologyDose-Response Relationship, DrugGlycolipids/metabolismMethyltransferases/genetics/metabolismMicrobial Sensitivity TestsMicrobial Viability/drug effects/geneticsPancreatic Elastase/metabolismPhenotypePlasmids/geneticsPseudomonas aeruginosa/ drug effects/metabolism/physiologyQuorum Sensing/ drug effects/physiologyRibosomes/ metabolismTransformation, Bacterial
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PMID: 17876004
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KOHLER, Thilo, DUMAS, Jean-Luc Claude, VAN DELDEN, Christian. Ribosome protection prevents azithromycin-mediated quorum-sensing modulation and stationary-phase killing of Pseudomonas aeruginosa. In: Antimicrobial Agents and Chemotherapy, 2007, vol. 51, n° 12, p. 4243-4248. https://archive-ouverte.unige.ch/unige:7387

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Deposited on : 2010-06-21

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