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

Cell Microbiol. 2019 Oct;21(10):e13076. doi: 10.1111/cmi.13076. Epub 2019 Jul 14.

Abstract

Pseudomonas aeruginosa, an opportunistic life-threatening human bacterial pathogen, employs quorum-sensing (QS) signal molecules to modulate virulence gene expression. 2-(2-hydroxyphenyl)-thiazole-4-carbaldehyde (IQS) is a recently identified QS signal that integrates the canonical lasR-type QS of P. aeruginosa and host phosphate stress response to fine-tune its virulence production for a successful infection. To address the role of IQS in pathogen-host interaction, we here present that IQS inhibits host cell growth and stimulates apoptosis in a dosage-dependent manner. By downregulating the telomere-protecting protein POT1 in host cells, IQS activates CHK1, CHK2, and p53 in an Ataxia telangiectasia mutated (ATM)/ATM and RAD3-related (ATR)-dependent manner and induces DNA damage response. Overexpression of POT1 in host cells presents a resistance to IQS treatment. These results suggest a pivotal role of IQS in host apoptosis, highlighting the complexity of pathogenesis mechanisms developed by P. aeruginosa during infection.

Keywords: DNA damage response; IQS; POT1; Pseudomonas aeruginosa; apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Bacterial Proteins / metabolism
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Checkpoint Kinase 1 / genetics
  • Checkpoint Kinase 1 / metabolism
  • Checkpoint Kinase 2 / genetics
  • Checkpoint Kinase 2 / metabolism
  • DNA Damage / drug effects
  • DNA Damage / genetics
  • Humans
  • Mice
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Proteolysis
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / metabolism*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / chemistry
  • Pseudomonas aeruginosa / pathogenicity*
  • Quorum Sensing
  • Shelterin Complex
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • POT1 protein, human
  • Phenols
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Thiazoles
  • Tumor Suppressor Protein p53
  • aeruginaldehyde
  • Checkpoint Kinase 2
  • CHEK1 protein, human
  • CHEK2 protein, human
  • Checkpoint Kinase 1