Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus

Nana Yang, Qiao Cao, Shuyang Hu, Chenchen Xu, Ke Fan, Feifei Chen, Cai Guang Yang, Haihua Liang, Min Wu, Taeok Bae, Lefu Lan

Research output: Contribution to journalArticle

Abstract

Intracellular protein degradation is essential for the survival of all organisms, but its role in interspecies interaction is unknown. Here, we show that the ClpXP protease of Pseudomonas aeruginosa suppresses its antimicrobial activity against Staphylococcus aureus, a common pathogen co-isolated with P. aeruginosa from polymicrobial human infections. Using proteomic, biochemical, and molecular genetic approaches, we found that this effect is due to the inhibitory effects of ClpXP on the quorum sensing (QS) of P. aeruginosa, mainly by degrading proteins (e.g., PhnA, PhnB, PqsR, and RhlI) which are critical for the production of QS signal molecules PQS and C4-HSL. We provide evidence that co-culturing with S. aureus induces a decrease in the activity of ClpXP in P. aeruginosa, an effect which was also achieved by the treatment of P. aeruginosa with N-acetylglucosamine (GlcNAc), a widespread chemical present on the surface of diverse cell types from bacteria to humans. These findings extend the range of biological events governed by proteolytic machinery to microbial community structure, thus also suggesting that a chemical-induced alteration of protein homeostasis is a mechanism for interspecies interactions.

Original languageEnglish (US)
JournalMolecular Microbiology
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • ClpXP
  • microbial interspecies interactions
  • proteolysis
  • Pseudomonas aeruginosa
  • quorum sensing

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Yang, N., Cao, Q., Hu, S., Xu, C., Fan, K., Chen, F., Yang, C. G., Liang, H., Wu, M., Bae, T., & Lan, L. (Accepted/In press). Alteration of protein homeostasis mediates the interaction of Pseudomonas aeruginosa with Staphylococcus aureus. Molecular Microbiology. https://doi.org/10.1111/mmi.14519