Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection

ABSTRACT There has been no prior application of matched metagenomics and metatranscriptomics in Clostridioides difficile infection (CDI) evaluating the role of fungi in CDI or identifying community functions that contribute to the development of this disease. We collected diarrheal stools from 49 in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David B. Stewart, Justin R. Wright, Maria Fowler, Christopher J. McLimans, Vasily Tokarev, Isabella Amaniera, Owen Baker, Hoi-Tong Wong, Jeff Brabec, Rebecca Drucker, Regina Lamendella
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Clostridioides difficile metagenomics metatranscriptomics microbiome mycobiome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b75e5addef4049a689dd3a3dc1a6bcdc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b75e5addef4049a689dd3a3dc1a6bcdc
record_format	dspace
spelling	oai:doaj.org-article:b75e5addef4049a689dd3a3dc1a6bcdc2021-11-15T15:22:27ZIntegrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection10.1128/mSphere.00454-192379-5042https://doaj.org/article/b75e5addef4049a689dd3a3dc1a6bcdc2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00454-19https://doaj.org/toc/2379-5042ABSTRACT There has been no prior application of matched metagenomics and metatranscriptomics in Clostridioides difficile infection (CDI) evaluating the role of fungi in CDI or identifying community functions that contribute to the development of this disease. We collected diarrheal stools from 49 inpatients (18 of whom tested positive for CDI) under stringent inclusion criteria. We utilized a tiered sequencing approach to identify enriched bacterial and fungal taxa, using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, with matched metagenomics and metatranscriptomics performed on a subset of the population. Distinct bacterial and fungal compositions distinguished CDI-positive and -negative patients, with the greatest differentiation between the cohorts observed based on bacterial metatranscriptomics. Bipartite network analyses demonstrated that Aspergillus and Penicillium taxa shared a strong positive relationship in CDI patients and together formed negative cooccurring relationships with several bacterial taxa, including the Oscillospira, Comamonadaceae, Microbacteriaceae, and Cytophagaceae. Metatranscriptomics revealed enriched pathways in CDI patients associated with biofilm production primarily driven by Escherichia coli and Pseudomonas, quorum-sensing proteins, and two-component systems related to functions such as osmotic regulation, linoleic acid metabolism, and flagellar assembly. Differential expression of functional pathways unveiled a mechanism by which the causal dysbiosis of CDI may self-perpetuate, potentially contributing to treatment failures. We propose that CDI has a distinct fungus-associated bacteriome, and this first description of metatranscriptomics in human subjects with CDI demonstrates that inflammation, osmotic changes, and biofilm production are key elements of CDI pathophysiology. IMPORTANCE Our data suggest a potential role for fungi in the most common nosocomial bacterial infection in the United States, introducing the concept of a transkingdom interaction between bacteria and fungi in this disease. We also provide the first direct measure of microbial community function in Clostridioides difficile infection using patient-derived tissue samples, revealing antibiotic-independent mechanisms by which C. difficile infection may resist a return to a healthy gut microbiome.David B. StewartJustin R. WrightMaria FowlerChristopher J. McLimansVasily TokarevIsabella AmanieraOwen BakerHoi-Tong WongJeff BrabecRebecca DruckerRegina LamendellaAmerican Society for MicrobiologyarticleClostridioides difficilemetagenomicsmetatranscriptomicsmicrobiomemycobiomeMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridioides difficile metagenomics metatranscriptomics microbiome mycobiome Microbiology QR1-502
spellingShingle	Clostridioides difficile metagenomics metatranscriptomics microbiome mycobiome Microbiology QR1-502 David B. Stewart Justin R. Wright Maria Fowler Christopher J. McLimans Vasily Tokarev Isabella Amaniera Owen Baker Hoi-Tong Wong Jeff Brabec Rebecca Drucker Regina Lamendella Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
description	ABSTRACT There has been no prior application of matched metagenomics and metatranscriptomics in Clostridioides difficile infection (CDI) evaluating the role of fungi in CDI or identifying community functions that contribute to the development of this disease. We collected diarrheal stools from 49 inpatients (18 of whom tested positive for CDI) under stringent inclusion criteria. We utilized a tiered sequencing approach to identify enriched bacterial and fungal taxa, using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, with matched metagenomics and metatranscriptomics performed on a subset of the population. Distinct bacterial and fungal compositions distinguished CDI-positive and -negative patients, with the greatest differentiation between the cohorts observed based on bacterial metatranscriptomics. Bipartite network analyses demonstrated that Aspergillus and Penicillium taxa shared a strong positive relationship in CDI patients and together formed negative cooccurring relationships with several bacterial taxa, including the Oscillospira, Comamonadaceae, Microbacteriaceae, and Cytophagaceae. Metatranscriptomics revealed enriched pathways in CDI patients associated with biofilm production primarily driven by Escherichia coli and Pseudomonas, quorum-sensing proteins, and two-component systems related to functions such as osmotic regulation, linoleic acid metabolism, and flagellar assembly. Differential expression of functional pathways unveiled a mechanism by which the causal dysbiosis of CDI may self-perpetuate, potentially contributing to treatment failures. We propose that CDI has a distinct fungus-associated bacteriome, and this first description of metatranscriptomics in human subjects with CDI demonstrates that inflammation, osmotic changes, and biofilm production are key elements of CDI pathophysiology. IMPORTANCE Our data suggest a potential role for fungi in the most common nosocomial bacterial infection in the United States, introducing the concept of a transkingdom interaction between bacteria and fungi in this disease. We also provide the first direct measure of microbial community function in Clostridioides difficile infection using patient-derived tissue samples, revealing antibiotic-independent mechanisms by which C. difficile infection may resist a return to a healthy gut microbiome.
format	article
author	David B. Stewart Justin R. Wright Maria Fowler Christopher J. McLimans Vasily Tokarev Isabella Amaniera Owen Baker Hoi-Tong Wong Jeff Brabec Rebecca Drucker Regina Lamendella
author_facet	David B. Stewart Justin R. Wright Maria Fowler Christopher J. McLimans Vasily Tokarev Isabella Amaniera Owen Baker Hoi-Tong Wong Jeff Brabec Rebecca Drucker Regina Lamendella
author_sort	David B. Stewart
title	Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
title_short	Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
title_full	Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
title_fullStr	Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
title_full_unstemmed	Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection
title_sort	integrated meta-omics reveals a fungus-associated bacteriome and distinct functional pathways in <named-content content-type="genus-species">clostridioides difficile</named-content> infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b75e5addef4049a689dd3a3dc1a6bcdc
work_keys_str_mv	AT davidbstewart integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT justinrwright integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT mariafowler integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT christopherjmclimans integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT vasilytokarev integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT isabellaamaniera integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT owenbaker integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT hoitongwong integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT jeffbrabec integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT rebeccadrucker integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection AT reginalamendella integratedmetaomicsrevealsafungusassociatedbacteriomeanddistinctfunctionalpathwaysinnamedcontentcontenttypegenusspeciesclostridioidesdifficilenamedcontentinfection
_version_	1718427972527980544

Integrated Meta-omics Reveals a Fungus-Associated Bacteriome and Distinct Functional Pathways in <named-content content-type="genus-species">Clostridioides difficile</named-content> Infection

Ejemplares similares