The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model.
The quorum sensing com system regulates pneumococcal colonisation and invasive disease in a pseudo-stratified airway tissue model.
复制标题
群体感应通信系统在伪分层气道组织模型中调节肺炎球菌定植和侵袭性疾病。
DOI：
10.1016/j.micres.2022.127297
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发表时间：
2023
影响因子：
6.7
通讯作者：
Albrich,WernerC
中科院分区：
文献类型：
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作者：
Kahlert,ChristianR;Nigg,Susanne;Onder,Lucas;Dijkman,Ronald;Diener,Liliane;Vidal,AnaGJop;Rodriguez,Regulo;Vernazza,Pietro;Thiel,Volker;Vidal,JorgeE;Albrich,WernerC
背景：群体感应系统在肺炎链球菌（Spn）定植和侵袭过程中的作用尚不清楚。方法建立具有搏动纤毛、粘液生成和紧密连接的分化人气道上皮（HAE）细胞的体外模型，研究Spn的定植和易位。将HAE细胞接种Spn野生型TIGR4 （wtSpn）或其等基因ΔcomCquorum传感缺陷突变体。结果与spn相比，ΔcomCmutant的定殖密度在6 h时较低，在19 h和30 h时较高。易位与定植密度呈负相关。接种肺炎球菌后，经上皮电阻（TEER）降低，并与易位增加相关。共聚焦成像显示wtSpn的微集落形成突出，而ΔcomC突变体的微集落结构解体。ΔcomC突变体比wtSpn表现出更大的细胞毒性，这表明细胞毒性可能不是导致易位的机制。wtSpn感染ΔcomCcompared后，炎症细胞因子包括NLRP3炎性小体相关IL-18的密度和时间依赖性增加。ComC失活与溶血素表达增加相关。结论comc系统允许较高的群体结构组织水平，导致微群体形成，增加早期殖民化和随后的易位。我们认为ComC失活释放出一种非常不同且可能更具毒性的表型，值得进一步研究。
Background:The effects of thecomquorum sensing system during colonisation and invasion ofStreptococcus pneumoniae(Spn) are poorly understood.MethodsWe developed anex vivomodel 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 ΔcomCquorum sensing-deficient mutant.ResultsColonisation density of ΔcomCmutant was lower after 6 h but higher at 19 h and 30 h compared towtSpn. 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 ΔcomCcompared with wtSpn. ComC inactivation was associated with increased pneumolysin expression.ConclusionsComC 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.