The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model.

Autor: Kahlert CR; Division of Infectious Diseases & Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland; Children's Hospital of Eastern Switzerland, Infectious Disease & Hospital Epidemiology, St. Gallen, Switzerland. Electronic address: christian.kahlert@kispisg.ch., Nigg S; Division of Infectious Diseases & Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland., Onder L; Institute of Immunobiology, Cantonal Hospital St. Gallen, Switzerland., Dijkman R; Institute for Infectious Diseases, University of Bern, Bern, Switzerland., Diener L; Empa, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, Switzerland., Vidal AGJ; Department of Cell and Molecular Biology, and Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA., Rodriguez R; Institute of Pathology, Cantonal Hospital St. Gallen, Switzerland., Vernazza P; Division of Infectious Diseases & Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland., Thiel V; Institute of Virology and Immunology, Bern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland., Vidal JE; Department of Cell and Molecular Biology, and Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS, USA., Albrich WC; Division of Infectious Diseases & Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland. Electronic address: werner.albrich@kssg.ch.
Jazyk: angličtina
Zdroj: Microbiological research [Microbiol Res] 2023 Mar; Vol. 268, pp. 127297. Date of Electronic Publication: 2022 Dec 31.
DOI: 10.1016/j.micres.2022.127297
Abstrakt: Background: The effects of the com quorum sensing system during colonisation and invasion of Streptococcus pneumoniae (Spn) are poorly understood.
Methods: We developed an ex vivo model of differentiated human airway epithelial (HAE) cells with beating ciliae, mucus production and tight junctions to study Spn colonisation and translocation. HAE cells were inoculated with Spn wild-type TIGR4 (wtSpn) or its isogenic ΔcomC quorum sensing-deficient mutant.
Results: Colonisation density of ΔcomC mutant was lower after 6 h but higher at 19 h and 30 h compared to wtSpn. Translocation correlated inversely with colonisation density. Transepithelial electric resistance (TEER) decreased after pneumococcal inoculation and correlated with increased translocation. Confocal imaging illustrated prominent microcolony formation with wtSpn but disintegration of microcolony structures with ΔcomC mutant. ΔcomC mutant showed greater cytotoxicity than wtSpn, suggesting that cytotoxicity was likely not the mechanism leading to translocation. There was greater density- and time-dependent increase of inflammatory cytokines including NLRP3 inflammasome-related IL-18 after infection with ΔcomC compared with wtSpn. ComC inactivation was associated with increased pneumolysin expression.
Conclusions: ComC system allows a higher organisational level of population structure resulting in microcolony formation, increased early colonisation and subsequent translocation. We propose that ComC inactivation unleashes a very different and possibly more virulent phenotype that merits further investigation.
Competing Interests: Conflict of interest No potential conflicts of interest.
(Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: