Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts

ABSTRACT Neisseria meningitidis (meningococcus) can cause meningococcal disease, a rapidly progressing and often fatal disease that can occur in previously healthy children. Meningococci are found in healthy carriers, where they reside in the nasopharynx as commensals. While carriage is relatively c...

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Autores principales:	Xiaoyun Ren, David A. Eccles, Gabrielle A. Greig, Jane Clapham, Nicole E. Wheeler, Stinus Lindgreen, Paul P. Gardner, Joanna K. MacKichan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Neisseria meningitidis type IV pili carriage household contact Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8bb1289837d14ce8a488114c57fb30b3
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spelling	oai:doaj.org-article:8bb1289837d14ce8a488114c57fb30b32021-12-02T18:15:43ZGenomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts10.1128/mSystems.00127-172379-5077https://doaj.org/article/8bb1289837d14ce8a488114c57fb30b32017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00127-17https://doaj.org/toc/2379-5077ABSTRACT Neisseria meningitidis (meningococcus) can cause meningococcal disease, a rapidly progressing and often fatal disease that can occur in previously healthy children. Meningococci are found in healthy carriers, where they reside in the nasopharynx as commensals. While carriage is relatively common, invasive disease, associated with hypervirulent strains, is a comparatively rare event. The basis of increased virulence in some strains is not well understood. New Zealand suffered a protracted meningococcal disease epidemic, from 1991 to 2008. During this time, a household carriage study was carried out in Auckland: household contacts of index meningococcal disease patients were swabbed for isolation of carriage strains. In many households, healthy carriers harbored strains identical, as determined by laboratory typing, to the ones infecting the associated patient. We carried out more-detailed analyses of carriage and disease isolates from a select number of households. We found that isolates, although indistinguishable by laboratory typing methods and likely closely related, had many differences. We identified multiple genome variants and transcriptional differences between isolates. These studies enabled the identification of two new phase-variable genes. We also found that several carriage strains had lost their type IV pili and that this loss correlated with reduced tumor necrosis factor alpha (TNF-α) expression when cultured with epithelial cells. While nonpiliated meningococcal isolates have been previously found in carriage strains, this is the first evidence of an association between type IV pili from meningococci and a proinflammatory epithelial response. We also identified potentially important metabolic differences between carriage and disease isolates, including the sulfate assimilation pathway. IMPORTANCE Neisseria meningitidis causes meningococcal disease but is frequently carried in the throats of healthy individuals; the factors that determine whether invasive disease develops are not completely understood. We carried out detailed studies of isolates, collected from patients and their household contacts, to identify differences between commensal throat isolates and those that caused invasive disease. Though isolates were identical by laboratory typing methods, we uncovered many differences in their genomes, in gene expression, and in their interactions with host cells. In particular, we found that several carriage isolates had lost their type IV pili, a surprising finding since pili are often described as essential for colonization. However, loss of type IV pili correlated with reduced secretion of a proinflammatory cytokine, TNF-α, when meningococci were cocultured with human bronchial epithelial cells; hence, the loss of pili could provide an advantage to meningococci, by resulting in a dampened localized host immune response.Xiaoyun RenDavid A. EcclesGabrielle A. GreigJane ClaphamNicole E. WheelerStinus LindgreenPaul P. GardnerJoanna K. MacKichanAmerican Society for MicrobiologyarticleNeisseria meningitidistype IV pilicarriagehousehold contactMicrobiologyQR1-502ENmSystems, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neisseria meningitidis type IV pili carriage household contact Microbiology QR1-502
spellingShingle	Neisseria meningitidis type IV pili carriage household contact Microbiology QR1-502 Xiaoyun Ren David A. Eccles Gabrielle A. Greig Jane Clapham Nicole E. Wheeler Stinus Lindgreen Paul P. Gardner Joanna K. MacKichan Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
description	ABSTRACT Neisseria meningitidis (meningococcus) can cause meningococcal disease, a rapidly progressing and often fatal disease that can occur in previously healthy children. Meningococci are found in healthy carriers, where they reside in the nasopharynx as commensals. While carriage is relatively common, invasive disease, associated with hypervirulent strains, is a comparatively rare event. The basis of increased virulence in some strains is not well understood. New Zealand suffered a protracted meningococcal disease epidemic, from 1991 to 2008. During this time, a household carriage study was carried out in Auckland: household contacts of index meningococcal disease patients were swabbed for isolation of carriage strains. In many households, healthy carriers harbored strains identical, as determined by laboratory typing, to the ones infecting the associated patient. We carried out more-detailed analyses of carriage and disease isolates from a select number of households. We found that isolates, although indistinguishable by laboratory typing methods and likely closely related, had many differences. We identified multiple genome variants and transcriptional differences between isolates. These studies enabled the identification of two new phase-variable genes. We also found that several carriage strains had lost their type IV pili and that this loss correlated with reduced tumor necrosis factor alpha (TNF-α) expression when cultured with epithelial cells. While nonpiliated meningococcal isolates have been previously found in carriage strains, this is the first evidence of an association between type IV pili from meningococci and a proinflammatory epithelial response. We also identified potentially important metabolic differences between carriage and disease isolates, including the sulfate assimilation pathway. IMPORTANCE Neisseria meningitidis causes meningococcal disease but is frequently carried in the throats of healthy individuals; the factors that determine whether invasive disease develops are not completely understood. We carried out detailed studies of isolates, collected from patients and their household contacts, to identify differences between commensal throat isolates and those that caused invasive disease. Though isolates were identical by laboratory typing methods, we uncovered many differences in their genomes, in gene expression, and in their interactions with host cells. In particular, we found that several carriage isolates had lost their type IV pili, a surprising finding since pili are often described as essential for colonization. However, loss of type IV pili correlated with reduced secretion of a proinflammatory cytokine, TNF-α, when meningococci were cocultured with human bronchial epithelial cells; hence, the loss of pili could provide an advantage to meningococci, by resulting in a dampened localized host immune response.
format	article
author	Xiaoyun Ren David A. Eccles Gabrielle A. Greig Jane Clapham Nicole E. Wheeler Stinus Lindgreen Paul P. Gardner Joanna K. MacKichan
author_facet	Xiaoyun Ren David A. Eccles Gabrielle A. Greig Jane Clapham Nicole E. Wheeler Stinus Lindgreen Paul P. Gardner Joanna K. MacKichan
author_sort	Xiaoyun Ren
title	Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
title_short	Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
title_full	Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
title_fullStr	Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
title_full_unstemmed	Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts
title_sort	genomic, transcriptomic, and phenotypic analyses of <italic toggle="yes">neisseria meningitidis</italic> isolates from disease patients and their household contacts
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/8bb1289837d14ce8a488114c57fb30b3
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Genomic, Transcriptomic, and Phenotypic Analyses of <italic toggle="yes">Neisseria meningitidis</italic> Isolates from Disease Patients and Their Household Contacts

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