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B 群脑膜炎奈瑟菌在人血中生长的转录谱分析：一种疫苗抗原发现方法。

Transcriptional profiling of serogroup B Neisseria meningitidis growing in human blood: an approach to vaccine antigen discovery.

机构信息

Section of Paediatrics, Department of Medicine, Imperial College London, St. Mary's Campus, London, United Kingdom.

出版信息

PLoS One. 2012;7(6):e39718. doi: 10.1371/journal.pone.0039718. Epub 2012 Jun 22.

DOI:10.1371/journal.pone.0039718
PMID:22745818
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3382141/
Abstract

Neisseria meningitidis is a nasopharyngeal commensal of humans which occasionally invades the blood to cause septicaemia. The transcriptome of N. meningitidis strain MC58 grown in human blood for up to 4 hours was determined and around 10% of the genome was found to be differentially regulated. The nuo, pet and atp operons, involved in energy metabolism, were up-regulated, while many house-keeping genes were down-regulated. Genes encoding protein chaperones and proteases, involved in the stress response; complement resistant genes encoding enzymes for LOS sialylation and biosynthesis; and fHbp (NMB1870) and nspA (NMB0663), encoding vaccine candidates, were all up-regulated. Genes for glutamate uptake and metabolism, and biosynthesis of purine and pyrimidine were also up-regulated. Blood grown meningococci are under stress and undergo a metabolic adaptation and energy conservation strategy. The localisation of four putative outer membrane proteins encoded by genes found to be up-regulated in blood was assessed by FACS using polyclonal mouse antisera, and one (NMB0390) showed evidence of surface expression, supporting its vaccine candidacy.

摘要

脑膜炎奈瑟菌是人类鼻咽部的共生菌，偶尔会侵入血液引起败血症。本研究测定了在人血中培养长达 4 小时的脑膜炎奈瑟菌 MC58 菌株的转录组，发现约 10%的基因组受到差异调控。参与能量代谢的 nuo、pet 和 atp 操纵子上调，而许多管家基因下调。编码与应激反应相关的蛋白伴侣和蛋白酶的基因、参与 LOS 唾液酸化和生物合成的耐补体基因编码酶、以及 fHbp（NMB1870）和 nspA（NMB0663）等疫苗候选基因均上调。谷氨酸摄取和代谢以及嘌呤和嘧啶生物合成的基因也上调。血液中生长的脑膜炎球菌受到压力，经历代谢适应和能量保存策略。通过使用多克隆鼠抗血清的流式细胞术评估了在血液中上调的基因编码的四个假定外膜蛋白的定位，其中一个（NMB0390）显示出表面表达的证据，支持其疫苗候选资格。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/dea716d9d07f/pone.0039718.g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/ad468c239c8d/pone.0039718.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/5718c60818ec/pone.0039718.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/bcacd4cf12f4/pone.0039718.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/82b47231600a/pone.0039718.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/5fd9baccd676/pone.0039718.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/dea716d9d07f/pone.0039718.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/1776859113ee/pone.0039718.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/6288ba76aff5/pone.0039718.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/ad468c239c8d/pone.0039718.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/5718c60818ec/pone.0039718.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/bcacd4cf12f4/pone.0039718.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/82b47231600a/pone.0039718.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/5fd9baccd676/pone.0039718.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c327/3382141/dea716d9d07f/pone.0039718.g008.jpg

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