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. |