A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge

ABSTRACT Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid fa...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sandra G. Morrison, Amanda M. Giebel, Evelyn Toh, Arkaprabha Banerjee, David E. Nelson, Richard P. Morrison
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Chlamydia animal models genital tract immunity intracellular pathogen pathogenesis virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/db749f5c194844359773b2161f9ac76a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:db749f5c194844359773b2161f9ac76a
record_format	dspace
spelling	oai:doaj.org-article:db749f5c194844359773b2161f9ac76a2021-11-15T15:55:43ZA Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge10.1128/mBio.02770-202150-7511https://doaj.org/article/db749f5c194844359773b2161f9ac76a2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02770-20https://doaj.org/toc/2150-7511ABSTRACT Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum. Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease. IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.Sandra G. MorrisonAmanda M. GiebelEvelyn TohArkaprabha BanerjeeDavid E. NelsonRichard P. MorrisonAmerican Society for MicrobiologyarticleChlamydiaanimal modelsgenital tract immunityintracellular pathogenpathogenesisvirulenceMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chlamydia animal models genital tract immunity intracellular pathogen pathogenesis virulence Microbiology QR1-502
spellingShingle	Chlamydia animal models genital tract immunity intracellular pathogen pathogenesis virulence Microbiology QR1-502 Sandra G. Morrison Amanda M. Giebel Evelyn Toh Arkaprabha Banerjee David E. Nelson Richard P. Morrison A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
description	ABSTRACT Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum. Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease. IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.
format	article
author	Sandra G. Morrison Amanda M. Giebel Evelyn Toh Arkaprabha Banerjee David E. Nelson Richard P. Morrison
author_facet	Sandra G. Morrison Amanda M. Giebel Evelyn Toh Arkaprabha Banerjee David E. Nelson Richard P. Morrison
author_sort	Sandra G. Morrison
title	A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
title_short	A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
title_full	A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
title_fullStr	A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
title_full_unstemmed	A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge
title_sort	genital infection-attenuated <named-content content-type="genus-species">chlamydia muridarum</named-content> mutant infects the gastrointestinal tract and protects against genital tract challenge
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/db749f5c194844359773b2161f9ac76a
work_keys_str_mv	AT sandragmorrison agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT amandamgiebel agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT evelyntoh agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT arkaprabhabanerjee agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT davidenelson agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT richardpmorrison agenitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT sandragmorrison genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT amandamgiebel genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT evelyntoh genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT arkaprabhabanerjee genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT davidenelson genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge AT richardpmorrison genitalinfectionattenuatednamedcontentcontenttypegenusspecieschlamydiamuridarumnamedcontentmutantinfectsthegastrointestinaltractandprotectsagainstgenitaltractchallenge
_version_	1718427182805549056

A Genital Infection-Attenuated <named-content content-type="genus-species">Chlamydia muridarum</named-content> Mutant Infects the Gastrointestinal Tract and Protects against Genital Tract Challenge

Ejemplares similares