Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host

ABSTRACT A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropi...

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Autores principales:	Brad Griesenauer, Tuan M. Tran, Kate R. Fortney, Diane M. Janowicz, Paula Johnson, Hongyu Gao, Stephen Barnes, Landon S. Wilson, Yunlong Liu, Stanley M. Spinola
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	dual RNA-seq Haemophilus ducreyi human infection model interactome metabolome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2726edf7257247edb5c22f9847c85876
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spelling	oai:doaj.org-article:2726edf7257247edb5c22f9847c858762021-11-15T15:55:23ZDetermination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host10.1128/mBio.01193-192150-7511https://doaj.org/article/2726edf7257247edb5c22f9847c858762019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01193-19https://doaj.org/toc/2150-7511ABSTRACT A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found that in vivo H. ducreyi transcripts were distinct from those in the inocula, as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were found to be involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggest that H. ducreyi exploits the metabolic niche created by the host immune response. IMPORTANCE Dual RNA sequencing (RNA-seq) offers the promise of determining an interactome at a transcriptional level between a bacterium and the host but has yet to be done on any bacterial infection in human tissue. We performed dual RNA-seq and metabolomics analyses on wounded and infected sites following experimental infection of the arm with H. ducreyi. Our results suggest that H. ducreyi survives in an abscess by utilizing l-ascorbate as an alternative carbon source, possibly taking advantage of host ascorbic acid recycling, and that H. ducreyi also adapts by upregulating genes involved in anaerobic metabolism and inorganic ion and nutrient transport. To our knowledge, this is the first description of an interaction network between a bacterium and the human host at a site of infection.Brad GriesenauerTuan M. TranKate R. FortneyDiane M. JanowiczPaula JohnsonHongyu GaoStephen BarnesLandon S. WilsonYunlong LiuStanley M. SpinolaAmerican Society for Microbiologyarticledual RNA-seqHaemophilus ducreyihuman infection modelinteractomemetabolomeMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	dual RNA-seq Haemophilus ducreyi human infection model interactome metabolome Microbiology QR1-502
spellingShingle	dual RNA-seq Haemophilus ducreyi human infection model interactome metabolome Microbiology QR1-502 Brad Griesenauer Tuan M. Tran Kate R. Fortney Diane M. Janowicz Paula Johnson Hongyu Gao Stephen Barnes Landon S. Wilson Yunlong Liu Stanley M. Spinola Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
description	ABSTRACT A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found that in vivo H. ducreyi transcripts were distinct from those in the inocula, as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were found to be involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggest that H. ducreyi exploits the metabolic niche created by the host immune response. IMPORTANCE Dual RNA sequencing (RNA-seq) offers the promise of determining an interactome at a transcriptional level between a bacterium and the host but has yet to be done on any bacterial infection in human tissue. We performed dual RNA-seq and metabolomics analyses on wounded and infected sites following experimental infection of the arm with H. ducreyi. Our results suggest that H. ducreyi survives in an abscess by utilizing l-ascorbate as an alternative carbon source, possibly taking advantage of host ascorbic acid recycling, and that H. ducreyi also adapts by upregulating genes involved in anaerobic metabolism and inorganic ion and nutrient transport. To our knowledge, this is the first description of an interaction network between a bacterium and the human host at a site of infection.
format	article
author	Brad Griesenauer Tuan M. Tran Kate R. Fortney Diane M. Janowicz Paula Johnson Hongyu Gao Stephen Barnes Landon S. Wilson Yunlong Liu Stanley M. Spinola
author_facet	Brad Griesenauer Tuan M. Tran Kate R. Fortney Diane M. Janowicz Paula Johnson Hongyu Gao Stephen Barnes Landon S. Wilson Yunlong Liu Stanley M. Spinola
author_sort	Brad Griesenauer
title	Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
title_short	Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
title_full	Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
title_fullStr	Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
title_full_unstemmed	Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
title_sort	determination of an interaction network between an extracellular bacterial pathogen and the human host
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2726edf7257247edb5c22f9847c85876
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Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host

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