A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes

ABSTRACT Listeria monocytogenes can cause a life-threatening illness when the foodborne pathogen spreads beyond the intestinal tract to distant organs. Many aspects of the intestinal phase of L. monocytogenes pathogenesis remain unknown. Here, we present a foodborne infection model using C57BL/6 mic...

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Autores principales:	Alexander Louie, Ting Zhang, Simone Becattini, Matthew K. Waldor, Daniel A. Portnoy
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Listeria monocytogenes STAMP gastrointestinal infection intracellular bacteria pathogenesis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/996b1beff94b476b8164a44aebde9aa6
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spelling	oai:doaj.org-article:996b1beff94b476b8164a44aebde9aa62021-11-15T15:54:47ZA Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes10.1128/mBio.02948-192150-7511https://doaj.org/article/996b1beff94b476b8164a44aebde9aa62019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02948-19https://doaj.org/toc/2150-7511ABSTRACT Listeria monocytogenes can cause a life-threatening illness when the foodborne pathogen spreads beyond the intestinal tract to distant organs. Many aspects of the intestinal phase of L. monocytogenes pathogenesis remain unknown. Here, we present a foodborne infection model using C57BL/6 mice that have been pretreated with streptomycin. In this model, as few as 100 L. monocytogenes CFU were required to cause self-limiting enterocolitis, and systemic dissemination followed previously reported routes. Using this model, we report that listeriolysin O (LLO) and actin assembly-inducing protein (ActA), two critical virulence determinants, were necessary for intestinal pathology and systemic spread but were dispensable for intestinal growth. Sequence tag-based analysis of microbial populations (STAMP) was used to investigate the within-host population dynamics of wild-type and LLO-deficient strains. The wild-type bacterial population experienced severe bottlenecks over the course of infection, and by 5 days, the intestinal population was highly enriched for bacteria originating from the gallbladder. In contrast, LLO-deficient strains did not efficiently disseminate and gain access to the gallbladder, and the intestinal population remained diverse. These findings suggest that systemic spread and establishment of a bacterial reservoir in the gallbladder imparts an intraspecies advantage in intestinal occupancy. Since intestinal L. monocytogenes is ultimately released into the environment, within-host population bottlenecks may provide purifying selection of virulence genes. IMPORTANCE Listeria monocytogenes maintains capabilities for free-living growth in the environment and for intracellular replication in a wide range of hosts, including livestock and humans. Here, we characterized an enterocolitis model of foodborne L. monocytogenes infection. This work highlights a multiorgan trafficking circuit and reveals a fitness advantage for bacteria that successfully complete this cycle. Because virulence factors play critical roles in systemic dissemination and multiple bottlenecks occur as the bacterial population colonizes different tissue sites, this multiorgan trafficking circuit likely provides purifying selection of virulence genes. This study also serves as a foundation for future work using the L. monocytogenes-induced enterocolitis model to investigate the biology of L. monocytogenes in the intestinal environment.Alexander LouieTing ZhangSimone BecattiniMatthew K. WaldorDaniel A. PortnoyAmerican Society for MicrobiologyarticleListeria monocytogenesSTAMPgastrointestinal infectionintracellular bacteriapathogenesisMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Listeria monocytogenes STAMP gastrointestinal infection intracellular bacteria pathogenesis Microbiology QR1-502
spellingShingle	Listeria monocytogenes STAMP gastrointestinal infection intracellular bacteria pathogenesis Microbiology QR1-502 Alexander Louie Ting Zhang Simone Becattini Matthew K. Waldor Daniel A. Portnoy A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
description	ABSTRACT Listeria monocytogenes can cause a life-threatening illness when the foodborne pathogen spreads beyond the intestinal tract to distant organs. Many aspects of the intestinal phase of L. monocytogenes pathogenesis remain unknown. Here, we present a foodborne infection model using C57BL/6 mice that have been pretreated with streptomycin. In this model, as few as 100 L. monocytogenes CFU were required to cause self-limiting enterocolitis, and systemic dissemination followed previously reported routes. Using this model, we report that listeriolysin O (LLO) and actin assembly-inducing protein (ActA), two critical virulence determinants, were necessary for intestinal pathology and systemic spread but were dispensable for intestinal growth. Sequence tag-based analysis of microbial populations (STAMP) was used to investigate the within-host population dynamics of wild-type and LLO-deficient strains. The wild-type bacterial population experienced severe bottlenecks over the course of infection, and by 5 days, the intestinal population was highly enriched for bacteria originating from the gallbladder. In contrast, LLO-deficient strains did not efficiently disseminate and gain access to the gallbladder, and the intestinal population remained diverse. These findings suggest that systemic spread and establishment of a bacterial reservoir in the gallbladder imparts an intraspecies advantage in intestinal occupancy. Since intestinal L. monocytogenes is ultimately released into the environment, within-host population bottlenecks may provide purifying selection of virulence genes. IMPORTANCE Listeria monocytogenes maintains capabilities for free-living growth in the environment and for intracellular replication in a wide range of hosts, including livestock and humans. Here, we characterized an enterocolitis model of foodborne L. monocytogenes infection. This work highlights a multiorgan trafficking circuit and reveals a fitness advantage for bacteria that successfully complete this cycle. Because virulence factors play critical roles in systemic dissemination and multiple bottlenecks occur as the bacterial population colonizes different tissue sites, this multiorgan trafficking circuit likely provides purifying selection of virulence genes. This study also serves as a foundation for future work using the L. monocytogenes-induced enterocolitis model to investigate the biology of L. monocytogenes in the intestinal environment.
format	article
author	Alexander Louie Ting Zhang Simone Becattini Matthew K. Waldor Daniel A. Portnoy
author_facet	Alexander Louie Ting Zhang Simone Becattini Matthew K. Waldor Daniel A. Portnoy
author_sort	Alexander Louie
title	A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
title_short	A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
title_full	A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
title_fullStr	A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
title_full_unstemmed	A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes
title_sort	multiorgan trafficking circuit provides purifying selection of <named-content content-type="genus-species">listeria monocytogenes</named-content> virulence genes
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/996b1beff94b476b8164a44aebde9aa6
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A Multiorgan Trafficking Circuit Provides Purifying Selection of <named-content content-type="genus-species">Listeria monocytogenes</named-content> Virulence Genes

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