Kahlert, Christian R; Nigg, Susanne; Onder, Lucas; Dijkman, Ronald; Diener, Liliane; Vidal, Ana G Jop; Rodriguez, Regulo; Vernazza, Pietro; Thiel, Volker; Vidal, Jorge E; Albrich, Werner C (2023). The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model. Microbiological research, 268, p. 127297. Elsevier 10.1016/j.micres.2022.127297
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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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) |
UniBE Contributor: |
Dijkman, Ronald, Thiel, Volker Earl |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health 600 Technology > 630 Agriculture |
ISSN: |
1618-0623 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 Jan 2023 09:41 |
Last Modified: |
23 Jan 2023 00:16 |
Publisher DOI: |
10.1016/j.micres.2022.127297 |
PubMed ID: |
36608536 |
Uncontrolled Keywords: |
Colonisations Human bronchial epithelial cell culture model Invasion Pathogenesis Pneumococcus Quorum sensing |
BORIS DOI: |
10.48350/177040 |
URI: |
https://boris.unibe.ch/id/eprint/177040 |
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