<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization

ABSTRACT Susceptibility to Clostridium difficile infection (CDI) is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistent C. difficile in...

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Autores principales:	Matthew L. Jenior, Jhansi L. Leslie, Vincent B. Young, Patrick D. Schloss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	16S rRNA gene sequencing Clostridium difficile colonization resistance machine learning microbiome systems biology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0403f747c60a4011b82638beadbfcd0a
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spelling	oai:doaj.org-article:0403f747c60a4011b82638beadbfcd0a2021-11-15T15:24:22Z<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization10.1128/mSphere.00261-182379-5042https://doaj.org/article/0403f747c60a4011b82638beadbfcd0a2018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00261-18https://doaj.org/toc/2379-5042ABSTRACT Susceptibility to Clostridium difficile infection (CDI) is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistent C. difficile infection. As such, we utilized a mouse model of infection to explore the effect of distinct antibiotic classes on the impact that infection has on community-level transcription and metabolic signatures shortly following pathogen colonization and how those changes may associate with persistence of C. difficile. Untargeted metabolomic analysis revealed that C. difficile infection had significantly larger impacts on the metabolic environment across cefoperazone- and streptomycin-pretreated mice, which became persistently colonized compared to clindamycin-pretreated mice, where infection quickly became undetectable. Through metagenome-enabled metatranscriptomics, we observed that transcripts for genes associated with carbon and energy acquisition were greatly reduced in infected animals, suggesting that those niches were instead occupied by C. difficile. Furthermore, the largest changes in transcription were seen in the least abundant species, indicating that C. difficile may “attack the loser” in gut environments where sustained infection occurs more readily. Overall, our results suggest that C. difficile is able to restructure the nutrient-niche landscape in the gut to promote persistent infection. IMPORTANCE Clostridium difficile has become the most common single cause of hospital-acquired infection over the last decade in the United States. Colonization resistance to the nosocomial pathogen is primarily provided by the gut microbiota, which is also involved in clearing the infection as the community recovers from perturbation. As distinct antibiotics are associated with different risk levels for CDI, we utilized a mouse model of infection with 3 separate antibiotic pretreatment regimens to generate alternative gut microbiomes that each allowed for C. difficile colonization but varied in clearance rate. To assess community-level dynamics, we implemented an integrative multi-omics approach that revealed that infection significantly changed many aspects of the gut community. The degree to which the community changed was inversely correlated with clearance during the first 6 days of infection, suggesting that C. difficile differentially modifies the gut environment to promote persistence. This is the first time that metagenome-enabled metatranscriptomics have been employed to study the behavior of a host-associated microbiota in response to an infection. Our results allow for a previously unseen understanding of the ecology associated with C. difficile infection and provide the groundwork for identification of context-specific probiotic therapies.Matthew L. JeniorJhansi L. LeslieVincent B. YoungPatrick D. SchlossAmerican Society for Microbiologyarticle16S rRNA gene sequencingClostridium difficilecolonization resistancemachine learningmicrobiomesystems biologyMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	16S rRNA gene sequencing Clostridium difficile colonization resistance machine learning microbiome systems biology Microbiology QR1-502
spellingShingle	16S rRNA gene sequencing Clostridium difficile colonization resistance machine learning microbiome systems biology Microbiology QR1-502 Matthew L. Jenior Jhansi L. Leslie Vincent B. Young Patrick D. Schloss <italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
description	ABSTRACT Susceptibility to Clostridium difficile infection (CDI) is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistent C. difficile infection. As such, we utilized a mouse model of infection to explore the effect of distinct antibiotic classes on the impact that infection has on community-level transcription and metabolic signatures shortly following pathogen colonization and how those changes may associate with persistence of C. difficile. Untargeted metabolomic analysis revealed that C. difficile infection had significantly larger impacts on the metabolic environment across cefoperazone- and streptomycin-pretreated mice, which became persistently colonized compared to clindamycin-pretreated mice, where infection quickly became undetectable. Through metagenome-enabled metatranscriptomics, we observed that transcripts for genes associated with carbon and energy acquisition were greatly reduced in infected animals, suggesting that those niches were instead occupied by C. difficile. Furthermore, the largest changes in transcription were seen in the least abundant species, indicating that C. difficile may “attack the loser” in gut environments where sustained infection occurs more readily. Overall, our results suggest that C. difficile is able to restructure the nutrient-niche landscape in the gut to promote persistent infection. IMPORTANCE Clostridium difficile has become the most common single cause of hospital-acquired infection over the last decade in the United States. Colonization resistance to the nosocomial pathogen is primarily provided by the gut microbiota, which is also involved in clearing the infection as the community recovers from perturbation. As distinct antibiotics are associated with different risk levels for CDI, we utilized a mouse model of infection with 3 separate antibiotic pretreatment regimens to generate alternative gut microbiomes that each allowed for C. difficile colonization but varied in clearance rate. To assess community-level dynamics, we implemented an integrative multi-omics approach that revealed that infection significantly changed many aspects of the gut community. The degree to which the community changed was inversely correlated with clearance during the first 6 days of infection, suggesting that C. difficile differentially modifies the gut environment to promote persistence. This is the first time that metagenome-enabled metatranscriptomics have been employed to study the behavior of a host-associated microbiota in response to an infection. Our results allow for a previously unseen understanding of the ecology associated with C. difficile infection and provide the groundwork for identification of context-specific probiotic therapies.
format	article
author	Matthew L. Jenior Jhansi L. Leslie Vincent B. Young Patrick D. Schloss
author_facet	Matthew L. Jenior Jhansi L. Leslie Vincent B. Young Patrick D. Schloss
author_sort	Matthew L. Jenior
title	<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
title_short	<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
title_full	<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
title_fullStr	<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
title_full_unstemmed	<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization
title_sort	<italic toggle="yes">clostridium difficile</italic> alters the structure and metabolism of distinct cecal microbiomes during initial infection to promote sustained colonization
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/0403f747c60a4011b82638beadbfcd0a
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<italic toggle="yes">Clostridium difficile</italic> Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization

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