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Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis

Author

Listed:
  • Kayla A. Simanek

    (University at Albany, School of Public Health)

  • Megan L. Schumacher

    (University at Albany, School of Public Health)

  • Caleb P. Mallery

    (University at Albany, School of Public Health)

  • Stella Shen

    (New York State Department of Health)

  • Lingyun Li

    (New York State Department of Health)

  • Jon E. Paczkowski

    (University at Albany, School of Public Health
    New York State Department of Health)

Abstract

Quorum sensing is a mechanism of bacterial communication that controls virulence gene expression. Pseudomonas aeruginosa regulates virulence via two synthase/transcription factor receptor pairs: LasI/R and RhlI/R. LasR is considered the master transcriptional regulator of quorum sensing, as it upregulates rhlI/R. However, clinical isolates often have inactivating mutations in lasR, while maintaining Rhl-dependent signaling. We sought to understand how quorum sensing progresses in isolates with lasR mutations, specifically via activation of RhlR. We find that clinical isolates with lasR inactivating mutations often harbor concurrent mutations in rhlI. Using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we discover that strains lacking lasR overproduce the RhlI-synthesized autoinducer and that RhlI variants re-calibrate autoinducer concentrations to wild-type levels, restoring virulent phenotypes. These findings provide a mechanism for the plasticity of quorum sensing progression in an acute infection niche.

Suggested Citation

  • Kayla A. Simanek & Megan L. Schumacher & Caleb P. Mallery & Stella Shen & Lingyun Li & Jon E. Paczkowski, 2023. "Quorum-sensing synthase mutations re-calibrate autoinducer concentrations in clinical isolates of Pseudomonas aeruginosa to enhance pathogenesis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43702-4
    DOI: 10.1038/s41467-023-43702-4
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    1. Kelei Zhao & Xiting Yang & Qianglin Zeng & Yige Zhang & Heyue Li & Chaochao Yan & Jing Shirley Li & Huan Liu & Liangming Du & Yi Wu & Gui Huang & Ting Huang & Yamei Zhang & Hui Zhou & Xinrong Wang & Y, 2023. "Evolution of lasR mutants in polymorphic Pseudomonas aeruginosa populations facilitates chronic infection of the lung," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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