Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis.
Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis.
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DOI：
10.1099/mgen.0.000103
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发表时间：
2017-01
影响因子：
3.9
通讯作者：
Bentley SD
中科院分区：
文献类型：
--
作者：
Lees JA;Kremer PHC;Manso AS;Croucher NJ;Ferwerda B;Serón MV;Oggioni MR;Parkhill J;Brouwer MC;van der Ende A;van de Beek D;Bentley SD
最近的研究为病原体基因组的快速多样化提供了证据，其中一些可能会影响疾病的进程。我们以前曾描述过在细菌性脑膜炎病例中感染单个患者血液和脑脊液（CSF）的分离株之间所见的这种变异。在这里，我们对869名脑膜炎患者的血液和脑脊液中的成对分离物进行了全基因组测序，以确定在细菌性脑膜炎病例中，这两个生态位之间是否经常发生这种变异。使用无参考变异调用方法的组合，我们发现两种主要病原体肺炎链球菌和脑膜炎奈瑟菌在细菌性脑膜炎期间的任何入侵生态位都没有发生遗传适应。因此，这项研究表明，能够引起脑膜炎的细菌在进入血液时已经能够做到这一点，并且不需要进一步改变序列来穿过血脑屏障。我们的研究结果将重点放在了细菌在鼻咽部携带和入侵之间的进化，或者宿主的多样性，作为决定入侵的可能机制。
Recent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species, Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the blood–brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion, or diversity of the host, as likely mechanisms for determining invasiveness.