Flagella-mediated cytosolic motility of Salmonella enterica Paratyphi A aids in evasion of xenophagy but does not impact egress from host cells,Molecular Microbiology

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Flagella-mediated cytosolic motility of Salmonella enterica Paratyphi A aids in evasion of xenophagy but does not impact egress from host cells
Molecular Microbiology ( IF 2.6 ) Pub Date : 2023-06-06 , DOI: 10.1111/mmi.15104
Felix Scharte ₁ , Rico Franzkoch _{1,

2} , Michael Hensel _{1,

3}

Affiliation

Salmonella enterica is a common foodborne, facultative intracellular enteropathogen. Typhoidal serovars like Paratyphi A (SPA) are human restricted and cause severe systemic diseases, while many serovars like Typhimurium (STM) have a broad host range, and usually lead to self-limiting gastroenteritis. There are key differences between typhoidal and non-typhoidal Salmonella in pathogenesis, but underlying mechanisms remain largely unknown. Transcriptomes and phenotypes in epithelial cells revealed induction of motility, flagella and chemotaxis genes for SPA but not STM. SPA exhibited cytosolic motility mediated by flagella. In this study, we applied single-cell microscopy to analyze triggers and cellular consequences of cytosolic motility. Live-cell imaging (LCI) revealed that SPA invades host cells in a highly cooperative manner. Extensive membrane ruffling at invasion sites led to increased membrane damage in nascent Salmonella-containing vacuole, and subsequent cytosolic release. After release into the cytosol, motile bacteria showed the same velocity as under culture conditions in media. Reduced capture of SPA by autophagosomal membranes was observed by LCI and electron microscopy. Prior work showed that SPA does not use flagella-mediated motility for cell exit via the intercellular spread. However, cytosolic motile SPA was invasion-primed if released from host cells. Our results reveal flagella-mediated cytosolic motility as a possible xenophagy evasion mechanism that could drive disease progression and contributes to the dissemination of systemic infection.

中文翻译：

肠沙门氏菌甲型副伤寒菌鞭毛介导的胞质运动有助于逃避异体吞噬，但不影响宿主细胞的排出

肠道沙门氏菌是一种常见的食源性兼性细胞内肠道病原体。甲型副伤寒 (SPA) 等伤寒血清型是人类限制性的，可引起严重的全身性疾病，而鼠伤寒 (STM) 等许多血清型具有广泛的宿主范围，通常会导致自限性胃肠炎。伤寒沙门氏菌和非伤寒沙门氏菌在发病机制上存在重大差异，但潜在的机制仍然很大程度上未知。上皮细胞的转录组和表型显示 SPA 能诱导运动、鞭毛和趋化基因，但 STM 则不然。 SPA表现出由鞭毛介导的细胞质运动。在这项研究中，我们应用单细胞显微镜来分析细胞质运动的触发因素和细胞后果。活细胞成像（LCI）显示 SPA 以高度协作的方式侵入宿主细胞。入侵部位的广泛膜皱褶导致新生含沙门氏菌液泡的膜损伤增加，以及随后的胞质释放。释放到细胞质中后，运动细菌表现出与在培养基中培养条件下相同的速度。 LCI 和电子显微镜观察到自噬体膜对 SPA 的捕获减少。先前的研究表明，SPA 不使用鞭毛介导的运动来通过细胞间扩散进行细胞退出。然而，如果从宿主细胞中释放，胞质运动性 SPA 就会引发侵袭。我们的结果揭示了鞭毛介导的细胞质运动作为一种可能的异体吞噬逃避机制，可以驱动疾病进展并有助于全身感染的传播。

更新日期：2023-06-06

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