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01-12-2019 | Pseudomonas Aeruginosa | Original Investigation

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

Authors: Pradeep Kumar Singh, Vivek Kumar Yadav, Manmohit Kalia, Deepmala Sharma, Deepak Pandey, Vishnu Agarwal

Published in: Medical Microbiology and Immunology | Issue 6/2019

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 expected to provide a better understanding of the role of C12 in P. aeruginosa pathogenesis.

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Title: Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling
Authors: Pradeep Kumar Singh
Vivek Kumar Yadav
Manmohit Kalia
Deepmala Sharma
Deepak Pandey
Vishnu Agarwal
Publication date: 01-12-2019
Publisher: Springer Berlin Heidelberg
Keyword: Pseudomonas Aeruginosa
Published in: Medical Microbiology and Immunology / Issue 6/2019
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI: https://doi.org/10.1007/s00430-019-00631-8

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

Abstract

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