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ShlA toxin of Serratia induces P2Y2- and α5β1-dependent autophagy and bacterial clearance from host cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2023 Sep; Vol. 299 (9), pp. 105119. Date of Electronic Publication: 2023 Jul 30. - Publication Year :
- 2023
-
Abstract
- Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely dependent on the ShlA toxin. Once Serratia invades the eukaryotic cell and multiples inside an intracellular vacuole, ShlA expression also promotes an exocytic event that allows bacterial egress from the host cell without compromising its integrity. Several toxins, including ShlA, were shown to induce ATP efflux from eukaryotic cells. Here, we demonstrate that ShlA triggered a nonlytic release of ATP from Chinese hamster ovary (CHO) cells. Enzymatic removal of accumulated extracellular ATP (eATP) or pharmacological blockage of the eATP-P2Y2 purinergic receptor inhibited the ShlA-promoted autophagic response in CHO cells. Despite the intrinsic ecto-ATPase activity of CHO cells, the effective concentration and kinetic profile of eATP was consistent with the established affinity of the P2Y2 receptor and the known kinetics of autophagy induction. Moreover, eATP removal or P2Y2 receptor inhibition also suppressed the ShlA-induced exocytic expulsion of the bacteria from the host cell. Blocking α5β1 integrin highly inhibited ShlA-dependent autophagy, a result consistent with α5β1 transactivation by the P2Y2 receptor. In sum, eATP operates as the key signaling molecule that allows the eukaryotic cell to detect the challenge imposed by the contact with the ShlA toxin. Stimulation of P2Y2-dependent pathways evokes the activation of a defensive response to counteract cell damage and promotes the nonlytic clearance of the pathogen from the infected cell.<br />Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cricetinae
Adenosine Triphosphate metabolism
CHO Cells
Cricetulus
Exocytosis drug effects
Humans
Autophagy drug effects
Host-Pathogen Interactions drug effects
Integrin alpha5beta1 antagonists & inhibitors
Integrin alpha5beta1 metabolism
Receptors, Purinergic P2Y2 metabolism
Serratia chemistry
Serratia drug effects
Serratia physiology
Toxins, Biological pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 299
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 37527778
- Full Text :
- https://doi.org/10.1016/j.jbc.2023.105119