Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues

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dc.contributor.authorShi-qi An
dc.contributor.authorGupta, Manoj k.
dc.contributor.authorTang, Ji-liang
dc.contributor.authorTwomey, Kate B.
dc.contributor.authorO’Sullivan, Timothy P.
dc.date.accessioned2023-05-01T17:36:01Z
dc.date.available2023-05-01T17:36:01Z
dc.date.issued2019
dc.description.abstractPseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced autophosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/1057
dc.language.isoenen_US
dc.publisherNature Communicationsen_US
dc.titleModulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analoguesen_US
dc.typeArticleen_US
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