首页> 外文期刊>The Journal of Infectious Diseases >A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells.
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A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells.

机译:乳酸脱氢酶在淋病奈瑟氏菌在人多形核白细胞和宫颈上皮细胞中的存活中的作用。

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摘要

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.
机译:乳酸是一种丰富的代谢产物,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。在奈瑟氏菌属的情况下,已经证明了乳酸通透酶在宿主定植中的重要性,但是在后基因组时代,致病性奈瑟氏菌中乳酸代谢的研究很少。我们在这里描述了专心的人类病原体淋病奈瑟氏球菌的基因组注释,呼吸和底物水平的乳酸脱氢酶(LDHs)的表征。使用淋病奈瑟氏球菌1291野生型和等基因突变菌株的生化分析表明,胞质LdhA(NAD(+)依赖性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的突变体在嗜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,使用建立良好的人原代宫颈上皮细胞模型对宿主定植的分析表明,两种呼吸酶对宿主微需氧环境的定植和存活具有重要作用。综上所述,这些数据表明宿主来源的乳酸对于淋病奈瑟氏球菌在人细胞中的生长和存活至关重要。

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