Lubin Jean-Bernard, Lewis Warren G, Gilbert Nicole M, Weimer Cory M, Almagro-Moreno Salvador, Boyd E Fidelma, Lewis Amanda L
Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Infect Immun. 2015 Aug;83(8):3126-36. doi: 10.1128/IAI.00345-15. Epub 2015 May 26.
Sialic acids are found on all vertebrate cell surfaces and are part of a larger class of molecules known as nonulosonic acids. Many bacterial pathogens synthesize related nine-carbon backbone sugars; however, the role(s) of these non-sialic acid molecules in host-pathogen interactions is poorly understood. Vibrio vulnificus is the leading cause of seafood-related death in the United States due to its ability to quickly access the host bloodstream, which it can accomplish through gastrointestinal or wound infection. However, little is known about how this organism persists systemically. Here we demonstrate that sialic acid-like molecules are present on the lipopolysaccharide of V. vulnificus, are required for full motility and biofilm formation, and also contribute to the organism's natural resistance to polymyxin B. Further experiments in a murine model of intravenous V. vulnificus infection demonstrated that expression of nonulosonic acids had a striking benefit for bacterial survival during bloodstream infection and dissemination to other tissues in vivo. In fact, levels of bacterial persistence in the blood corresponded to the overall levels of these molecules expressed by V. vulnificus isolates. Taken together, these results suggest that molecules similar to sialic acids evolved to facilitate the aquatic lifestyle of V. vulnificus but that their emergence also resulted in a gain of function with life-threatening potential in the human host.
唾液酸存在于所有脊椎动物的细胞表面，是一类被称为非ulosonic酸的更大分子类别的一部分。许多细菌病原体合成相关的九碳骨架糖；然而，这些非唾液酸分子在宿主 - 病原体相互作用中的作用尚不清楚。创伤弧菌是美国与海鲜相关死亡的主要原因，因为它能够迅速进入宿主血液，这可以通过胃肠道或伤口感染来实现。然而，对于这种生物体如何在全身持续存在知之甚少。在这里，我们证明了唾液酸样分子存在于创伤弧菌的脂多糖上，是完全运动性和生物膜形成所必需的，并且还有助于该生物体对多粘菌素B的天然抗性。在静脉注射创伤弧菌感染的小鼠模型中进行的进一步实验表明，非ulosonic酸的表达对血流感染期间的细菌存活以及体内向其他组织的传播具有显著益处。事实上，血液中细菌持续存在的水平与创伤弧菌分离株表达的这些分子的总体水平相对应。综上所述，这些结果表明，类似于唾液酸的分子进化是为了促进创伤弧菌的水生生活方式，但它们的出现也导致了在人类宿主中具有危及生命潜力的功能获得。
