Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-L-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling

Medical Microbiology and Immunology
Pradeep Kumar SinghVishnu Agarwal

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that utilizes the quorum-sensing (QS) process to regulate the production of different virulence factors and biofilm. N-3-oxo-dodecanoyl-L-homoserine lactone (C12) is a key QS molecule of P. aeruginosa which interacts with the mammalian immune cells and modulates their function. Here, we investigated the molecular mechanism of C12-induced apoptosis in neutrophils. Our data show that C12 causes apoptosis in neutrophils through an elevation in cytosolic and mitochondrial Ca2+ levels. Besides, C12 induces phosphatidylserine (PS) exposure, mitochondrial membrane potential (MMP) depolarization, mitochondrial permeability transition pore (MPTP) formation and mitochondrial reactive oxygen species (mROS) generation. C12-induced rise in intracellular Ca2+ level is majorly contributed by endoplasmic reticulum store through the activation of inositol 1, 4, 5-triphosphate receptor. Intracellular calcium chelation inhibited C12-induced mitochondrial dysfunction and apoptosis. Further, inhibition of mitochondrial Ca2+ uniporter by ruthenium red or Ru360 abrogated C12-induced mitochondrial Ca2+ uptake, MMP loss, MPTP opening, mROS production, and PS exposure. These mechanistic insights are ex...Continue Reading

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BETA
flow
flow cytometry

Software Mentioned

FlowJo
GraphPad Prism

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