A Role for Lactate Dehydrogenases in the Survival of Neisseria gonorrhoeae in Human Polymorphonuclear Leukocytes and Cervical Epithelial Cells
A Role for Lactate Dehydrogenases in the Survival of Neisseria gonorrhoeae in Human Polymorphonuclear Leukocytes and Cervical Epithelial Cells
复制标题
DOI：
10.1093/infdis/jiu230
复制
发表时间：
2014-10-15
影响因子：
6.4
通讯作者：
McEwan, Alastair G.
中科院分区：
文献类型：
--
作者：
Atack, John M.;Ibranovic, Ines;McEwan, Alastair G.
乳酸是一种丰富的代谢物，由宿主组织和共生生物产生，是细菌病原体重要的潜在碳源。以奈瑟菌为例，乳酸渗透酶在宿主定植中的重要性已经得到证实，但在后基因组时代，关于致病性奈瑟菌乳酸代谢的研究很少。我们在此描述基因组注释的特征，呼吸和底物水平乳酸脱氢酶（LDHs）从专性人类病原体淋病奈瑟菌。对淋病奈球菌1291野生型和等基因突变株进行生化检测，结果表明细胞质LdhA （NAD+依赖的d -乳酸脱氢酶）和膜结合呼吸酶LdhD （d -乳酸脱氢酶）和LldD （l -乳酸脱氢酶）正确注释。与野生型细胞相比，缺乏LdhA和LdhD的突变体在中性粒细胞中的存活率大大降低，这突出了d -乳酸代谢在淋球菌存活中的重要性。此外，利用成熟的人原代宫颈上皮细胞模型进行的宿主定植试验表明，这两种呼吸酶对宿主在微氧环境中的定植和存活有重要贡献。综上所述，这些数据表明，宿主来源的乳酸对于淋病奈瑟菌在人类细胞中的生长和存活至关重要。
Lactate is an abundant metabolite, produced by host tissues and commensal organisms, and it represents an important potential carbon source for bacterial pathogens. In the case of Neisseria spp., the importance of the lactate permease in colonization of the host has been demonstrated, but there have been few studies of lactate metabolism in pathogenic Neisseria in the postgenomic era. We describe herein the characterization of genome-annotated, respiratory, and substrate-level lactate dehydrogenases (LDHs) from the obligate human pathogen Neisseria gonorrhoeae. Biochemical assays using N. gonorrhoeae 1291 wild type and isogenic mutant strains showed that cytoplasmic LdhA (NAD+-dependent D-lactate dehydrogenase) and the membrane-bound respiratory enzymes, LdhD (D-lactate dehydrogenase) and LldD (L-lactate dehydrogenase) are correctly annotated. Mutants lacking LdhA and LdhD showed greatly reduced survival in neutrophils compared with wild type cells, highlighting the importance of D-lactate metabolism in gonococcal survival. Furthermore, an assay of host colonization using the well-established human primary cervical epithelial cell model revealed that the two respiratory enzymes make a significant contribution to colonization of and survival within the microaerobic environment of the host. Taken together, these data suggest that host-derived lactate is critical for the growth and survival of N. gonorrhoeae in human cells.