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.
© 2019 John Wiley & Sons Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A549 Cells
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Animals
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Apoptosis / drug effects*
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Apoptosis / genetics
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Bacterial Proteins / metabolism
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Cell Proliferation / drug effects
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Cell Proliferation / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Checkpoint Kinase 1 / genetics
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Checkpoint Kinase 1 / metabolism
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Checkpoint Kinase 2 / genetics
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Checkpoint Kinase 2 / metabolism
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DNA Damage / drug effects
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DNA Damage / genetics
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Humans
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Mice
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Phenols / chemistry
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Phenols / pharmacology*
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Proteolysis
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Pseudomonas Infections / genetics
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Pseudomonas Infections / metabolism*
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Pseudomonas Infections / microbiology
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Pseudomonas aeruginosa / chemistry
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Pseudomonas aeruginosa / pathogenicity*
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Quorum Sensing
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Shelterin Complex
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Telomere-Binding Proteins / genetics
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Telomere-Binding Proteins / metabolism*
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Thiazoles / chemistry
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Thiazoles / pharmacology*
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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Virulence / genetics
Substances
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Bacterial Proteins
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POT1 protein, human
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Phenols
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Shelterin Complex
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Telomere-Binding Proteins
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Thiazoles
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Tumor Suppressor Protein p53
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aeruginaldehyde
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Checkpoint Kinase 2
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CHEK1 protein, human
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CHEK2 protein, human
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Checkpoint Kinase 1