A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.
A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.
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DOI：
10.1126/sciadv.adi9834
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发表时间：
2023-11-10
期刊：
影响因子：
13.6
通讯作者：
Rohn JL
中科院分区：
文献类型：
--
作者：
Flores C;Ling J;Loh A;Maset RG;Aw A;White IJ;Fernando R;Rohn JL
尿路感染是全世界最常见的感染之一，通常在动物和具有有限尿路致病菌株的细胞系中进行研究。在这里，我们评估了人类尿路上皮微组织模型中的不同细菌种类，这些细菌表现出完全分层、分化、先天上皮反应和尿液耐受性。几种尿路病原体侵入细胞内，但共生大肠杆菌也侵入细胞内，这表明侵入是一种共同的生存策略，而不仅仅是毒力标志。大肠杆菌粘附素 FimH 是细胞内细菌群落形成所必需的，但不是入侵所必需的。其他共同的生活方式包括丝状（革兰氏阴性菌）、链状（革兰氏阳性菌）和脱落细胞的劫持，而生物膜样聚集体主要由假单胞菌和变形杆菌形成。尿路上皮细胞排出 Rab-/LC3 修饰结构中的侵入性细菌，而高细胞毒性/侵入性尿路病原体（但不是共生菌）会破坏宿主屏障功能并强烈诱导脱落和细胞因子产生。总体而言，这项工作强调了人类尿路上皮微环境中不同物种/菌株特异性感染策略和相应的宿主反应，提供了微组织、细胞和分子水平的见解。细菌在人类膀胱微组织模型中采用不同的相互作用策略，引发特定的宿主先天反应。
Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli, suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus. Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level. Bacteria deploy varied interaction strategies in a human bladder microtissue model, eliciting specific host innate responses.
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DOI：
10.1038/nrmicro3432
发表时间：
2015-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Flores-Mireles AL;Walker JN;Caparon M;Hultgren SJ
通讯作者：
Hultgren SJ
影响因子：
3.6
作者：
Bahrani-Mougeot, FK;Buckles, EL;Donnenberg, MS
通讯作者：
Donnenberg, MS
影响因子：
5.7
作者：
Demirel I;Persson A;Brauner A;Särndahl E;Kruse R;Persson K
通讯作者：
Persson K
影响因子：
3.8
作者：
Foroogh, Neamati;Rezvan, Moniri;Mahmood, Saffari
通讯作者：
Mahmood, Saffari
影响因子：
5.5
作者：
Gallo, Luciana, I;Dalghi, Marianela G.;Apodaca, Gerard
通讯作者：
Apodaca, Gerard