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Bacterial quorum-sensing signal IQS induces host cell apoptosis by targeting POT1-p53 signalling pathway

Jianhe Wang1,2, Chao Wang1,3, Hong-Bing Yu4,5

  • 1Guangdong Province Key Laboratory of Microbial Signals and Disease Control, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China.

Cellular Microbiology
|June 30, 2019
PubMed

Insights

Pseudomonas aeruginosa uses a signal molecule called IQS to control virulence. IQS inhibits host cell growth and triggers apoptosis by affecting the POT1 protein and DNA damage response.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Cell Biology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen that uses quorum-sensing (QS) to regulate virulence.
  • IQS is a novel QS signal molecule that links P. aeruginosa QS with host phosphate stress.
  • Understanding IQS's role in host-pathogen interaction is crucial for deciphering infection mechanisms.

Purpose of the Study:

  • To investigate the role of IQS in Pseudomonas aeruginosa pathogenesis.
  • To elucidate the mechanisms by which IQS affects host cells.
  • To determine the impact of IQS on host cell growth and apoptosis.

Main Methods:

  • Dosage-dependent analysis of IQS effects on host cell growth and apoptosis.
  • Investigation of IQS-mediated modulation of POT1, CHK1, CHK2, and p53.
  • Assessment of DNA damage response pathways, including ATM/ATR.
  • Evaluation of host cell resistance to IQS upon POT1 overexpression.

Main Results:

  • IQS inhibits host cell growth and induces apoptosis in a dose-dependent manner.
  • IQS downregulates the telomere-protecting protein POT1 in host cells.
  • IQS activates DNA damage response kinases (CHK1, CHK2) and p53 via ATM/ATR.
  • Overexpression of POT1 confers resistance to IQS-induced apoptosis.

Conclusions:

  • IQS plays a significant role in inducing host cell apoptosis during P. aeruginosa infection.
  • The IQS-mediated downregulation of POT1 is a key mechanism driving host cell apoptosis and DNA damage response.
  • These findings reveal a complex interplay between bacterial QS signals and host cell machinery, contributing to P. aeruginosa pathogenesis.
Keywords:
DNA damage responseIQSPOT1Pseudomonas aeruginosaapoptosis

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