Alpha-2,3-sialyltransferase enhances Neisseria gonorrhoeae survival during experimental murine genital tract infection.
Alpha-2,3-sialyltransferase enhances Neisseria gonorrhoeae survival during experimental murine genital tract infection.
复制标题
α-2,3-唾液酸转移酶可增强实验性小鼠生殖道感染期间淋病奈瑟菌的存活率。
DOI：
10.1128/iai.00433-06
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发表时间：
2006
影响因子：
3.1
通讯作者：
Jerse,AnnE
中科院分区：
文献类型：
--
作者：
Wu,Hong;Jerse,AnnE
在淋球菌中加入宿主来源的唾液酸被认为是淋球菌逃避宿主天然防御的重要机制。这一假说主要基于补体介导的体外实验和吞噬细胞杀伤实验。在这里，我们报道了一个非极性的α-2，3-唾液酸基转移酶(Lst)突变体。在与野生型淋菌株竞争感染期间，淋球菌在17-β雌二醇处理的雌性BALB/c小鼠的下生殖道定植能力显著减弱。突变的遗传互补使突变体恢复到野生型水平。对B10.D2-HCoH2dH2-T18c/OSN(C5缺乏)小鼠的研究表明，该突变的减弱并不是由于对补体介导的细菌溶解的敏感性增加，这一结果与最近报道的补体级联中的宿主限制一致。然而，LST缺陷淋球菌在正常小鼠体内注射后，比唾液酸化的野生型淋球菌更快地被杀死，这与唾液酸化对中性粒细胞(PMN)杀伤的保护作用是一致的。据报道，对于人类中性粒细胞，唾液酸化的淋球菌对小鼠中性粒细胞的杀伤作用更强，唾液酸化导致减少与雌激素处理的小鼠中性粒细胞呼吸爆发的关联和诱导。综上所述，这些研究表明唾液酸化具有生存优势。提高淋病小鼠对中性粒细胞杀伤的抵抗力。本报告首次直接证明了α-2，3-唾液酸基转移酶对Ton的贡献。淋病在活体模型中的发病机制。这项研究还验证了利用实验性小鼠感染来研究淋球菌致病机制的某些方面。
The addition of host-derived sialic acid toNeisseria gonorrhoeaelipooligosaccharide is hypothesized to be an important mechanism by which gonococci evade host innate defenses. This hypothesis is based primarily on in vitro assays of complement-mediated and phagocytic killing. Here we report that a nonpolar α-2,3-sialyltransferase (lst) mutant ofN. gonorrhoeaewas significantly attenuated in its capacity to colonize the lower genital tract of 17-β estradiol-treated female BALB/c mice during competitive infection with the wild-type strain. Genetic complementation of thelstmutation restored recovery of the mutant to wild-type levels. Studies with B10.D2-HCoH2dH2-T18c/OSN (C5-deficient) mice showed that attenuation of thelstmutant was not due to increased sensitivity to complement-mediated bacteriolysis, a result that is consistent with recently reported host restrictions in the complement cascade. However, Lst-deficient gonococci were killed more rapidly than sialylated wild-type gonococci following intraperitoneal injection into normal mice, which is consistent with sialylation conferring protection against killing by polymorphonuclear leukocytes (PMNs). As reported for human PMNs, sialylated gonococci were more resistant to killing by murine PMNs, and sialylation led to reduced association with and induction of a weaker respiratory burst in PMNs from estradiol-treated mice. In summary, these studies suggest sialylation confers a survival advantage toN. gonorrhoeaein mice by increasing resistance to PMN killing. This report is the first direct demonstration that α-2,3-sialyltransferase contributes toN. gonorrhoeaepathogenesis in an in vivo model. This study also validates the use of experimental murine infection to study certain aspects of gonococcal pathogenesis.