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

作者：Jianhe Wang, Chao Wang, Hongbing Yu, Stephen Dela Ahator, Xiaoyan Wu, Shumei Lv, Lian‐Hui Zhang · 发表于：Cellular Microbiology · 年份：2019 · DOI：10.1111/cmi.13076 · 被引用次数：24 · 研究领域：Bacterial biofilms and quorum sensing、Vibrio bacteria research studies、Clostridium difficile and Clostridium perfringens research

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.