Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen

ABSTRACT Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacter...

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Autores principales:	Katherine R. Hargreaves, Cesar O. Flores, Trevor D. Lawley, Martha R. J. Clokie
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/88bb06c6b06249f09013237401e1fa2b
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spelling	oai:doaj.org-article:88bb06c6b06249f09013237401e1fa2b2021-11-15T15:45:54ZAbundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen10.1128/mBio.01045-132150-7511https://doaj.org/article/88bb06c6b06249f09013237401e1fa2b2014-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01045-13https://doaj.org/toc/2150-7511ABSTRACT Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. IMPORTANCE Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an extra level of complexity in this predator-prey microbial system. Our results demonstrate that the impact of phage infection in this system is widespread and that the CRISPR/Cas system is likely to be an important aspect of the evolutionary dynamics in C. difficile.Katherine R. HargreavesCesar O. FloresTrevor D. LawleyMartha R. J. ClokieAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 5 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Katherine R. Hargreaves Cesar O. Flores Trevor D. Lawley Martha R. J. Clokie Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
description	ABSTRACT Clostridium difficile is an important human-pathogenic bacterium causing antibiotic-associated nosocomial infections worldwide. Mobile genetic elements and bacteriophages have helped shape C. difficile genome evolution. In many bacteria, phage infection may be controlled by a form of bacterial immunity called the clustered regularly interspaced short palindromic repeats/CRISPR-associated (CRISPR/Cas) system. This uses acquired short nucleotide sequences (spacers) to target homologous sequences (protospacers) in phage genomes. C. difficile carries multiple CRISPR arrays, and in this paper we examine the relationships between the host- and phage-carried elements of the system. We detected multiple matches between spacers and regions in 31 C. difficile phage and prophage genomes. A subset of the spacers was located in prophage-carried CRISPR arrays. The CRISPR spacer profiles generated suggest that related phages would have similar host ranges. Furthermore, we show that C. difficile strains of the same ribotype could either have similar or divergent CRISPR contents. Both synonymous and nonsynonymous mutations in the protospacer sequences were identified, as well as differences in the protospacer adjacent motif (PAM), which could explain how phages escape this system. This paper illustrates how the distribution and diversity of CRISPR spacers in C. difficile, and its prophages, could modulate phage predation for this pathogen and impact upon its evolution and pathogenicity. IMPORTANCE Clostridium difficile is a significant bacterial human pathogen which undergoes continual genome evolution, resulting in the emergence of new virulent strains. Phages are major facilitators of genome evolution in other bacterial species, and we use sequence analysis-based approaches in order to examine whether the CRISPR/Cas system could control these interactions across divergent C. difficile strains. The presence of spacer sequences in prophages that are homologous to phage genomes raises an extra level of complexity in this predator-prey microbial system. Our results demonstrate that the impact of phage infection in this system is widespread and that the CRISPR/Cas system is likely to be an important aspect of the evolutionary dynamics in C. difficile.
format	article
author	Katherine R. Hargreaves Cesar O. Flores Trevor D. Lawley Martha R. J. Clokie
author_facet	Katherine R. Hargreaves Cesar O. Flores Trevor D. Lawley Martha R. J. Clokie
author_sort	Katherine R. Hargreaves
title	Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
title_short	Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
title_full	Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
title_fullStr	Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
title_full_unstemmed	Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen
title_sort	abundant and diverse clustered regularly interspaced short palindromic repeat spacers in <named-content content-type="genus-species">clostridium difficile</named-content> strains and prophages target multiple phage types within this pathogen
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/88bb06c6b06249f09013237401e1fa2b
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Abundant and Diverse Clustered Regularly Interspaced Short Palindromic Repeat Spacers in <named-content content-type="genus-species">Clostridium difficile</named-content> Strains and Prophages Target Multiple Phage Types within This Pathogen

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