Department of Microbiology and Immunology, Indiana University, Indianapolis, Indiana, USA.
Infect Immun. 2012 Feb;80(2):679-87. doi: 10.1128/IAI.05826-11. Epub 2011 Dec 5.
Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.
哺乳动物细胞表面的糖缀合物在细胞间通讯和自我识别中发挥着重要作用。在人体组织中优先表达的唾液酸是 N-乙酰神经氨酸（Neu5Ac）。在一个称为分子模拟的过程中，许多细菌病原体在其细胞表面糖脂上缀合 Neu5Ac。Neu5Ac 掺入细菌糖脂中促进了细菌与宿主细胞受体 Siglecs 的相互作用。这些相互作用影响细菌的黏附、对血清杀伤和吞噬的抵抗力以及先天免疫反应。杜克雷嗜血杆菌是软下疳的病原体，其表达高度唾液酸化的脂寡糖（LOS）。然而，其 LOS 中 Neu5Ac 水平降低的 lst 突变体在人类志愿者中完全具有毒力。最近，在杜克雷嗜血杆菌中发现了第二个唾液酸转移酶基因（Hd0053），这增加了 Hd0053 在人类感染期间可能补偿 lst 缺失的可能性。CMP-Neu5Ac 是所有细菌唾液酸转移酶的必需核苷酸糖供体；来自杜克雷嗜血杆菌 CMP-Neu5Ac 合成酶（neuA）突变体的 LOS 没有可检测到的 Neu5Ac。在这里，我们在几种发病机制模型中比较了杜克雷嗜血杆菌 neuA 突变体与其野生型亲本。在人体接种实验中，neuA 突变体形成丘疹和脓疱的速度与其亲本没有不同。在含有和不含有 Neu5Ac 补充的培养基中生长时，neuA 突变体及其亲本在杀菌、巨噬细胞摄取和树突状细胞激活测定中具有相似的表型。尽管我们不能排除 LOS 唾液酸化对溃疡性疾病的贡献，但这些数据强烈表明，LOS 的唾液酸化对于杜克雷嗜血杆菌在人体中的发病机制是可有可无的。
