Jaishankar Jananee, Yang Hyojik, O'Keefe Ian P, Tenaglia Brandon M, Kinch Lisa N, Ernst Robert K, Orth Kim
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
HHMI, Dallas, TX 75390-9148.
Proc Natl Acad Sci U S A. 2025 Aug 19;122(33):e2426547122. doi: 10.1073/pnas.2426547122. Epub 2025 Aug 13.
(), a Gram-negative halophilic bacterium, is the leading cause of seafood-borne gastroenteritis. While the cytotoxic and enterotoxic capabilities of this bacterium have been previously investigated, the strategies it employs to circumvent innate immune detection by the host remain poorly understood. Bacterial lipopolysaccharide (LPS) serves as the major pathogen-associated molecular pattern that triggers host inflammatory responses, and its lipid A structure contributes to the degree of innate immune system activation. We sought to define the structure of the lipid A component of LPS in and probe its role in host innate immunity. Free living synthesizes a predominantly hepta-acylated lipid A structure, while also producing a minor subset of hexa-acylated lipid A. This altered acylated lipid A elicits a weakened TLR4 immune response as compared to , allowing entry and replication inside host cells. Deletion of the lipid A biosynthesis enzyme (VP0213) leads to a mutant strain with altered lipid A secondary acylation, enhanced immune response, and impaired replication within epithelial cells. This study provides evidence that the unique LPS structure synthesized by plays a crucial role in evading host innate immunity, facilitating the bacterium's survival and replication within host cells.
（某种革兰氏阴性嗜盐菌）是食源性肠胃炎的主要病因。虽然此前已对该细菌的细胞毒性和肠毒性能力进行过研究，但对于它规避宿主先天性免疫检测的策略仍知之甚少。细菌脂多糖（LPS）是触发宿主炎症反应的主要病原体相关分子模式，其脂质A结构影响先天性免疫系统的激活程度。我们试图确定该细菌中LPS的脂质A成分的结构，并探究其在宿主先天性免疫中的作用。自由生活的该细菌合成的主要是七酰化脂质A结构，同时也产生少量的六酰化脂质A。与（另一种细菌）相比，这种改变的酰化脂质A引发的TLR4免疫反应较弱，从而使该细菌能够进入宿主细胞并在其中复制。缺失该细菌脂质A生物合成酶（VP0213）会导致一种突变菌株，其脂质A二级酰化改变，免疫反应增强，且在上皮细胞内的复制受损。这项研究提供了证据，证明该细菌合成的独特LPS结构在逃避宿主先天性免疫、促进细菌在宿主细胞内存活和复制方面起着关键作用。
