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Title: Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis
Authors: Lees, John A.
Kremer, Philip H. C.
Manso, Ana S.
Croucher, Nicholas J.
Ferwerda, Bart
Serón, Mercedes Valls
Oggioni, Marco R.
Parkhill, Julian
Brouwer, Matthijs C.
van der Ende, Arie
van de Beek, Diederik
Bentley, Stephen D.
First Published: Jan-2017
Publisher: Microbiology Society
Citation: Microbial Genomics, 2017, 3, e000103
Abstract: 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.
DOI Link: 10.1099/mgen.0.000103
eISSN: 2057-5858
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Genetics

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