Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities

ABSTRACT In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university...

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Autores principales:	Sandeep J. Joseph, Nadav Topaz, How-Yi Chang, Melissa J. Whaley, Jeni T. Vuong, Alexander Chen, Fang Hu, Susanna E. Schmink, Laurel T. Jenkins, Lorraine D. Rodriguez-Rivera, Jennifer D. Thomas, Anna M. Acosta, Lucy McNamara, Heidi M. Soeters, Sarah Mbaeyi, Xin Wang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Neisseria meningitidis United States WGS carriage comparative genomics meningococcal Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f52749bebcd84d1bab2a2aa0bc54c975
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spelling	oai:doaj.org-article:f52749bebcd84d1bab2a2aa0bc54c9752021-11-15T15:29:16ZInsights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities10.1128/mSphere.00197-202379-5042https://doaj.org/article/f52749bebcd84d1bab2a2aa0bc54c9752020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00197-20https://doaj.org/toc/2379-5042ABSTRACT In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population. IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.Sandeep J. JosephNadav TopazHow-Yi ChangMelissa J. WhaleyJeni T. VuongAlexander ChenFang HuSusanna E. SchminkLaurel T. JenkinsLorraine D. Rodriguez-RiveraJennifer D. ThomasAnna M. AcostaLucy McNamaraHeidi M. SoetersSarah MbaeyiXin WangAmerican Society for MicrobiologyarticleNeisseria meningitidisUnited StatesWGScarriagecomparative genomicsmeningococcalMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neisseria meningitidis United States WGS carriage comparative genomics meningococcal Microbiology QR1-502
spellingShingle	Neisseria meningitidis United States WGS carriage comparative genomics meningococcal Microbiology QR1-502 Sandeep J. Joseph Nadav Topaz How-Yi Chang Melissa J. Whaley Jeni T. Vuong Alexander Chen Fang Hu Susanna E. Schmink Laurel T. Jenkins Lorraine D. Rodriguez-Rivera Jennifer D. Thomas Anna M. Acosta Lucy McNamara Heidi M. Soeters Sarah Mbaeyi Xin Wang Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
description	ABSTRACT In 2015 and 2016, meningococcal carriage evaluations were conducted at two universities in the United States following mass vaccination campaigns in response to Neisseria meningitidis serogroup B (NmB) disease outbreaks. A simultaneous carriage evaluation was also conducted at a university near one of the outbreaks, where no NmB cases were reported and no mass vaccination occurred. A total of ten cross-sectional carriage evaluation rounds were conducted, resulting in 1,514 meningococcal carriage isolates collected from 7,001 unique participants; 1,587 individuals were swabbed at multiple time points (repeat participants). All isolates underwent whole-genome sequencing. The most frequently observed clonal complexes (CC) were CC198 (27.3%), followed by CC1157 (17.4%), CC41/44 (9.8%), CC35 (7.4%), and CC32 (5.6%). Phylogenetic analysis identified carriage isolates that were highly similar to the NmB outbreak strains; comparative genomics between these outbreak and carriage isolates revealed genetic changes in virulence genes. Among repeat participants, 348 individuals carried meningococcal bacteria during at least one carriage evaluation round; 50.3% retained N. meningitidis carriage of a strain with the same sequence type (ST) and CC across rounds, 44.3% only carried N. meningitidis in one round, and 5.4% acquired a new N. meningitidis strain between rounds. Recombination, point mutations, deletions, and simple sequence repeats were the most frequent genetic mechanisms found in isolates collected from hosts carrying a strain of the same ST and CC across rounds. Our findings provide insight on the dynamics of meningococcal carriage among a population that is at higher risk for invasive meningococcal disease than the general population. IMPORTANCE U.S. university students are at a higher risk of invasive meningococcal disease than the general population. The responsible pathogen, Neisseria meningitidis, can be carried asymptomatically in the oropharynx; the dynamics of meningococcal carriage and the genetic features that distinguish carriage versus disease states are not completely understood. Through our analyses, we aimed to provide data to address these topics. We whole-genome sequenced 1,514 meningococcal carriage isolates from individuals at three U.S. universities, two of which underwent mass vaccination campaigns following recent meningococcal outbreaks. We describe the within-host genetic changes among individuals carrying a strain with the same molecular type over time, the primary strains being carried in this population, and the genetic differences between closely related outbreak and carriage strains. Our results provide detailed information on the dynamics of meningococcal carriage and the genetic differences in carriage and outbreak strains, which can inform future efforts to reduce the incidence of invasive meningococcal disease.
format	article
author	Sandeep J. Joseph Nadav Topaz How-Yi Chang Melissa J. Whaley Jeni T. Vuong Alexander Chen Fang Hu Susanna E. Schmink Laurel T. Jenkins Lorraine D. Rodriguez-Rivera Jennifer D. Thomas Anna M. Acosta Lucy McNamara Heidi M. Soeters Sarah Mbaeyi Xin Wang
author_facet	Sandeep J. Joseph Nadav Topaz How-Yi Chang Melissa J. Whaley Jeni T. Vuong Alexander Chen Fang Hu Susanna E. Schmink Laurel T. Jenkins Lorraine D. Rodriguez-Rivera Jennifer D. Thomas Anna M. Acosta Lucy McNamara Heidi M. Soeters Sarah Mbaeyi Xin Wang
author_sort	Sandeep J. Joseph
title	Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
title_short	Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
title_full	Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
title_fullStr	Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
title_full_unstemmed	Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities
title_sort	insights on population structure and within-host genetic changes among meningococcal carriage isolates from u.s. universities
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/f52749bebcd84d1bab2a2aa0bc54c975
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Insights on Population Structure and Within-Host Genetic Changes among Meningococcal Carriage Isolates from U.S. Universities

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