Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078

ABSTRACT Insights into the interaction between phages and their bacterial hosts are crucial for the development of phage therapy. However, only one study has investigated global gene expression of Clostridioides (formerly Clostridium) difficile carrying prophage, and transcriptional reprogramming du...

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Autores principales:	Tinghua Li, Yan Zhang, Ke Dong, Chih-Jung Kuo, Chong Li, Yong-Qiang Zhu, Jinhong Qin, Qing-Tian Li, Yung-Fu Chang, Xiaokui Guo, Yongzhang Zhu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Clostridioides difficile ribotype 078 bacteriophage RNA-seq bacteria-phage interaction transcriptome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e5f21d55d2ca45d0b2ad1fa3eafeca1b
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spelling	oai:doaj.org-article:e5f21d55d2ca45d0b2ad1fa3eafeca1b2021-12-02T19:47:39ZIsolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 07810.1128/mSystems.00017-202379-5077https://doaj.org/article/e5f21d55d2ca45d0b2ad1fa3eafeca1b2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00017-20https://doaj.org/toc/2379-5077ABSTRACT Insights into the interaction between phages and their bacterial hosts are crucial for the development of phage therapy. However, only one study has investigated global gene expression of Clostridioides (formerly Clostridium) difficile carrying prophage, and transcriptional reprogramming during lytic infection has not been studied. Here, we presented the isolation, propagation, and characterization of a newly discovered 35,109-bp phage, JD032, and investigated the global transcriptomes of both JD032 and C. difficile ribotype 078 (RT078) strain TW11 during JD032 infection. Transcriptome sequencing (RNA-seq) revealed the progressive replacement of bacterial host mRNA with phage transcripts. The expressed genes of JD032 were clustered into early, middle, and late temporal categories that were functionally similar. Specifically, a gene (JD032_orf016) involved in the lysis-lysogeny decision was identified as an early expression gene. Only 17.7% (668/3,781) of the host genes were differentially expressed, and more genes were downregulated than upregulated. The expression of genes involved in host macromolecular synthesis (DNA/RNA/proteins) was altered by JD032 at the level of transcription. In particular, the expression of the ropA operon was downregulated. Most noteworthy is that the gene expression of some antiphage systems, including CRISPR-Cas, restriction-modification, and toxin-antitoxin systems, was suppressed by JD032 during infection. In addition, bacterial sporulation, adhesion, and virulence factor genes were significantly downregulated. This study provides the first description of the interaction between anaerobic spore-forming bacteria and phages during lytic infection and highlights new aspects of C. difficile phage-host interactions. IMPORTANCE C. difficile is one of the most clinically significant intestinal pathogens. Although phages have been shown to effectively control C. difficile infection, the host responses to phage predation have not been fully studied. In this study, we reported the isolation and characterization of a new phage, JD032, and analyzed the global transcriptomic changes in the hypervirulent RT078 C. difficile strain, TW11, during phage JD032 infection. We found that bacterial host mRNA was progressively replaced with phage transcripts, three temporal categories of JD032 gene expression, the extensive interplay between phage-bacterium, antiphage-like responses of the host and phage evasion, and decreased expression of sporulation- and virulence-related genes of the host after phage infection. These findings confirmed the complexity of interactions between C. difficile and phages and suggest that phages undergoing a lytic cycle may also cause different phenotypes in hosts, similar to prophages, which may inspire phage therapy for the control of C. difficile.Tinghua LiYan ZhangKe DongChih-Jung KuoChong LiYong-Qiang ZhuJinhong QinQing-Tian LiYung-Fu ChangXiaokui GuoYongzhang ZhuAmerican Society for MicrobiologyarticleClostridioides difficileribotype 078bacteriophageRNA-seqbacteria-phage interactiontranscriptomeMicrobiologyQR1-502ENmSystems, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Clostridioides difficile ribotype 078 bacteriophage RNA-seq bacteria-phage interaction transcriptome Microbiology QR1-502
spellingShingle	Clostridioides difficile ribotype 078 bacteriophage RNA-seq bacteria-phage interaction transcriptome Microbiology QR1-502 Tinghua Li Yan Zhang Ke Dong Chih-Jung Kuo Chong Li Yong-Qiang Zhu Jinhong Qin Qing-Tian Li Yung-Fu Chang Xiaokui Guo Yongzhang Zhu Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
description	ABSTRACT Insights into the interaction between phages and their bacterial hosts are crucial for the development of phage therapy. However, only one study has investigated global gene expression of Clostridioides (formerly Clostridium) difficile carrying prophage, and transcriptional reprogramming during lytic infection has not been studied. Here, we presented the isolation, propagation, and characterization of a newly discovered 35,109-bp phage, JD032, and investigated the global transcriptomes of both JD032 and C. difficile ribotype 078 (RT078) strain TW11 during JD032 infection. Transcriptome sequencing (RNA-seq) revealed the progressive replacement of bacterial host mRNA with phage transcripts. The expressed genes of JD032 were clustered into early, middle, and late temporal categories that were functionally similar. Specifically, a gene (JD032_orf016) involved in the lysis-lysogeny decision was identified as an early expression gene. Only 17.7% (668/3,781) of the host genes were differentially expressed, and more genes were downregulated than upregulated. The expression of genes involved in host macromolecular synthesis (DNA/RNA/proteins) was altered by JD032 at the level of transcription. In particular, the expression of the ropA operon was downregulated. Most noteworthy is that the gene expression of some antiphage systems, including CRISPR-Cas, restriction-modification, and toxin-antitoxin systems, was suppressed by JD032 during infection. In addition, bacterial sporulation, adhesion, and virulence factor genes were significantly downregulated. This study provides the first description of the interaction between anaerobic spore-forming bacteria and phages during lytic infection and highlights new aspects of C. difficile phage-host interactions. IMPORTANCE C. difficile is one of the most clinically significant intestinal pathogens. Although phages have been shown to effectively control C. difficile infection, the host responses to phage predation have not been fully studied. In this study, we reported the isolation and characterization of a new phage, JD032, and analyzed the global transcriptomic changes in the hypervirulent RT078 C. difficile strain, TW11, during phage JD032 infection. We found that bacterial host mRNA was progressively replaced with phage transcripts, three temporal categories of JD032 gene expression, the extensive interplay between phage-bacterium, antiphage-like responses of the host and phage evasion, and decreased expression of sporulation- and virulence-related genes of the host after phage infection. These findings confirmed the complexity of interactions between C. difficile and phages and suggest that phages undergoing a lytic cycle may also cause different phenotypes in hosts, similar to prophages, which may inspire phage therapy for the control of C. difficile.
format	article
author	Tinghua Li Yan Zhang Ke Dong Chih-Jung Kuo Chong Li Yong-Qiang Zhu Jinhong Qin Qing-Tian Li Yung-Fu Chang Xiaokui Guo Yongzhang Zhu
author_facet	Tinghua Li Yan Zhang Ke Dong Chih-Jung Kuo Chong Li Yong-Qiang Zhu Jinhong Qin Qing-Tian Li Yung-Fu Chang Xiaokui Guo Yongzhang Zhu
author_sort	Tinghua Li
title	Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
title_short	Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
title_full	Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
title_fullStr	Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
title_full_unstemmed	Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078
title_sort	isolation and characterization of the novel phage jd032 and global transcriptomic response during jd032 infection of <named-content content-type="genus-species">clostridioides difficile</named-content> ribotype 078
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e5f21d55d2ca45d0b2ad1fa3eafeca1b
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Isolation and Characterization of the Novel Phage JD032 and Global Transcriptomic Response during JD032 Infection of <named-content content-type="genus-species">Clostridioides difficile</named-content> Ribotype 078

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