Plaza Nicolás, Pérez-Reytor Diliana, Corsini Gino, García Katherine, Urrutia Ítalo M
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8320000, Chile.
Microorganisms. 2024 Apr 17;12(4):813. doi: 10.3390/microorganisms12040813.
is an important human pathogen that is currently the leading cause of shellfish-borne gastroenteritis in the world. Particularly, the pandemic strain has the capacity to induce cytotoxicity and enterotoxicity through its Type 3 Secretion System (T3SS2) that leads to massive cell death. However, the specific mechanism by which the T3SS2 induces cell death remains unclear and its contribution to mitochondrial stress is not fully understood. In this work, we evaluated the contribution of the T3SS2 of in generating mitochondrial stress during infection in human intestinal HT-29 cells. To evaluate the contribution of the T3SS2 of in mitochondrial stress, infection assays were carried out to evaluate mitochondrial transition pore opening, mitochondrial fragmentation, ATP quantification, and cell viability during infection. Our results showed that the Δ1 (T3SS2+) mutant strain contributes to generating the sustained opening of the mitochondrial transition pore. Furthermore, it generates perturbations in the ATP production in infected cells, leading to a significant decrease in cell viability and loss of membrane integrity. Our results suggest that the T3SS2 from plays a role in generating mitochondrial stress that leads to cell death in human intestinal HT-29 cells. It is important to highlight that this study represents the first report indicating the possible role of the T3SS2 and its effector proteins involvement in generating mitochondrial stress, its impact on the mitochondrial pore, and its effect on ATP production in human cells.
是一种重要的人类病原体，目前是全球食源性肠胃炎的主要病因。特别是，大流行毒株能够通过其3型分泌系统（T3SS2）诱导细胞毒性和肠毒性，导致大量细胞死亡。然而，T3SS2诱导细胞死亡的具体机制仍不清楚，其对线粒体应激的作用也尚未完全了解。在这项工作中，我们评估了在感染人肠道HT-29细胞过程中，T3SS2对产生线粒体应激的作用。为了评估T3SS2在线粒体应激中的作用，我们进行了感染实验，以评估感染过程中线粒体通透性转换孔开放、线粒体碎片化、ATP定量和细胞活力。我们的结果表明，Δ1（T3SS2+）突变株有助于线粒体通透性转换孔的持续开放。此外，它还会对受感染细胞中的ATP产生造成干扰，导致细胞活力显著下降和膜完整性丧失。我们的结果表明，的T3SS2在产生线粒体应激中起作用，从而导致人肠道HT-29细胞死亡。需要强调的是，这项研究是首份表明T3SS2及其效应蛋白可能参与产生线粒体应激、对线粒体孔的影响以及对人类细胞中ATP产生的影响的报告。
