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

Author

Listed:
  • Shi-qi An

    (University of Southampton
    Queen’s University of Belfast)

  • Julie Murtagh

    (University College Cork)

  • Kate B. Twomey

    (University College Cork)

  • Manoj K. Gupta

    (University College Cork
    Central University of Haryana)

  • Timothy P. O’Sullivan

    (University College Cork
    University College Cork)

  • Rebecca Ingram

    (Queen’s University of Belfast)

  • Miguel A. Valvano

    (Queen’s University of Belfast)

  • Ji-liang Tang

    (Guangxi University)

Abstract

Pseudomonas 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 auto-phosphorylation 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.

Suggested Citation

  • Shi-qi An & Julie Murtagh & Kate B. Twomey & Manoj K. Gupta & Timothy P. O’Sullivan & Rebecca Ingram & Miguel A. Valvano & Ji-liang Tang, 2019. "Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies signal analogues," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10271-4
    DOI: 10.1038/s41467-019-10271-4
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    Cited by:

    1. Shengbo Wu & Jie Feng & Chunjiang Liu & Hao Wu & Zekai Qiu & Jianjun Ge & Shuyang Sun & Xia Hong & Yukun Li & Xiaona Wang & Aidong Yang & Fei Guo & Jianjun Qiao, 2022. "Machine learning aided construction of the quorum sensing communication network for human gut microbiota," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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