Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage

A scientist in our laboratory was accidentally infected while working with Z5463, a Neisseria meningitidis serogroup A strain. She developed severe symptoms (fever, meningism, purpuric lesions) that fortunately evolved with antibiotic treatment to complete recovery. Pulse-field gel electrophoresis c...

Full description

Bibliographic Details
Main Authors: Omer, H, Rose, G, Jolley, K, Frapy, E, Zahar, JR, Maiden, M, Bentley, S, Tinsley, C, Nassif, X, Bille, E
Format: Journal article
Language:English
Published: Public Library of Science 2011
_version_ 1826298049533575168
author Omer, H
Rose, G
Jolley, K
Frapy, E
Zahar, JR
Maiden, M
Bentley, S
Tinsley, C
Nassif, X
Bille, E
author_facet Omer, H
Rose, G
Jolley, K
Frapy, E
Zahar, JR
Maiden, M
Bentley, S
Tinsley, C
Nassif, X
Bille, E
author_sort Omer, H
collection OXFORD
description A scientist in our laboratory was accidentally infected while working with Z5463, a Neisseria meningitidis serogroup A strain. She developed severe symptoms (fever, meningism, purpuric lesions) that fortunately evolved with antibiotic treatment to complete recovery. Pulse-field gel electrophoresis confirmed that the isolate obtained from the blood culture (Z5463BC) was identical to Z5463, more precisely to a fourth subculture of this strain used the week before the contamination (Z5463PI). In order to get some insights into genomic modifications that can occur in vivo, we sequenced these three isolates. All the strains contained a mutated mutS allele and therefore displayed an hypermutator phenotype, consistent with the high number of mutations (SNP, Single Nucleotide Polymorphism) detected in the three strains. By comparing the number of SNP in all three isolates and knowing the number of passages between Z5463 and Z5463PI, we concluded that around 25 bacterial divisions occurred in the human body. As expected, the in vivo passage is responsible for several modifications of phase variable genes. This genomic study has been completed by transcriptomic and phenotypic studies, showing that the blood strain used a different haemoglobin-linked iron receptor (HpuA/B) than the parental strains (HmbR). Different pilin variants were found after the in vivo passage, which expressed different properties of adhesion. Furthermore the deletion of one gene involved in LOS biosynthesis (lgtB) results in Z5463BC expressing a different LOS than the L9 immunotype of Z2491. The in vivo passage, despite the small numbers of divisions, permits the selection of numerous genomic modifications that may account for the high capacity of the strain to disseminate.
first_indexed 2024-03-07T04:40:54Z
format Journal article
id oxford-uuid:d19a6dde-1ae9-4b20-b978-02363c1e8cd5
institution University of Oxford
language English
last_indexed 2024-03-07T04:40:54Z
publishDate 2011
publisher Public Library of Science
record_format dspace
spelling oxford-uuid:d19a6dde-1ae9-4b20-b978-02363c1e8cd52022-03-27T07:58:12ZGenotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passageJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d19a6dde-1ae9-4b20-b978-02363c1e8cd5EnglishSymplectic Elements at OxfordPublic Library of Science2011Omer, HRose, GJolley, KFrapy, EZahar, JRMaiden, MBentley, STinsley, CNassif, XBille, EA scientist in our laboratory was accidentally infected while working with Z5463, a Neisseria meningitidis serogroup A strain. She developed severe symptoms (fever, meningism, purpuric lesions) that fortunately evolved with antibiotic treatment to complete recovery. Pulse-field gel electrophoresis confirmed that the isolate obtained from the blood culture (Z5463BC) was identical to Z5463, more precisely to a fourth subculture of this strain used the week before the contamination (Z5463PI). In order to get some insights into genomic modifications that can occur in vivo, we sequenced these three isolates. All the strains contained a mutated mutS allele and therefore displayed an hypermutator phenotype, consistent with the high number of mutations (SNP, Single Nucleotide Polymorphism) detected in the three strains. By comparing the number of SNP in all three isolates and knowing the number of passages between Z5463 and Z5463PI, we concluded that around 25 bacterial divisions occurred in the human body. As expected, the in vivo passage is responsible for several modifications of phase variable genes. This genomic study has been completed by transcriptomic and phenotypic studies, showing that the blood strain used a different haemoglobin-linked iron receptor (HpuA/B) than the parental strains (HmbR). Different pilin variants were found after the in vivo passage, which expressed different properties of adhesion. Furthermore the deletion of one gene involved in LOS biosynthesis (lgtB) results in Z5463BC expressing a different LOS than the L9 immunotype of Z2491. The in vivo passage, despite the small numbers of divisions, permits the selection of numerous genomic modifications that may account for the high capacity of the strain to disseminate.
spellingShingle Omer, H
Rose, G
Jolley, K
Frapy, E
Zahar, JR
Maiden, M
Bentley, S
Tinsley, C
Nassif, X
Bille, E
Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title_full Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title_fullStr Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title_full_unstemmed Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title_short Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage
title_sort genotypic and phenotypic modifications of neisseria meningitidis after an accidental human passage
work_keys_str_mv AT omerh genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT roseg genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT jolleyk genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT frapye genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT zaharjr genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT maidenm genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT bentleys genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT tinsleyc genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT nassifx genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage
AT billee genotypicandphenotypicmodificationsofneisseriameningitidisafteranaccidentalhumanpassage