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Identification of Genes Involved in Neisseria meningitidis Colonization

机译：脑膜炎奈瑟氏球菌定殖相关基因的鉴定

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Neisseria meningitidis is a worldwide cause of meningitis and septicemia leading at least to 50,000 deaths every year. Nevertheless, N. meningitidis is also a commensal bacterium that asymptomatically colonizes the epithelial cells of the nasopharynx of 10 to 30% of healthy individuals. Occasionally, N. meningitidis crosses the nasopharyngeal barrier and enters the bloodstream. During bacteremia, N. meningitidis may adhere to endothelial cells of brain vessels and invade meninges. To identify the genes required for meningococcal host colonization, we screened a signature-tagged transposon mutagenesis library using an innovative in vitro colonization model in order to identify mutants displaying decreased capacity to colonize human epithelial cells. Approximately 1,600 defined insertion mutants of invasive serogroup C strain NEM8013 were screened. Candidate mutants were tested individually for quantification of bacterial biomass with confocal microscope and COMSTAT software. Five mutants were demonstrated to exhibit significantly decreased colonization ability. The identified genes, including narP and estD, appeared to be involved in adaptation to hypoxic conditions and stress resistance. Interestingly, the genes fadD1, nnrS, and NMV_2034 (encoding a putative thioredoxin), prior to this study, had not been shown to be involved in colonization. Therefore, we provide here insights into the meningococcal functions necessary for the bacterium to adapt to growth on host cells.
机译：脑膜炎奈瑟氏球菌是脑膜炎和败血病的全球性原因，每年至少导致50,000例死亡。然而，脑膜炎奈瑟氏菌也是一种共生细菌，其无症状地定殖在10％至30％的健康个体的鼻咽上皮细胞中。有时，脑膜炎奈瑟氏球菌会穿过鼻咽屏障并进入血液。在菌血症期间，脑膜炎奈瑟氏球菌可能粘附在脑血管的内皮细胞上并侵入脑膜。为了鉴定脑膜炎球菌宿主定殖所需的基因，我们使用创新的体外定殖模型筛选了带有特征标签的转座子诱变文库，以鉴定突变型人上皮细胞定殖能力下降。筛选了约1600个定义的侵入性血清群C株NEM8013的插入突变体。使用共聚焦显微镜和COMSTAT软件分别测试候选突变体的细菌生物量定量。证实了五个突变体表现出显着降低的定殖能力。鉴定出的基因，包括 narP 和 estD ，似乎参与了对低氧条件和抗逆性的适应。有趣的是，在这项研究之前，尚未证明基因 fadD1 ， nnrS 和 NMV_2034 （编码推定的硫氧还蛋白）是不相关的。在殖民地。因此，我们在这里提供了细菌适应宿主细胞生长所必需的脑膜炎球菌功能的见解。

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