Prophage Carriage and Diversity within Clinically Relevant Strains of Clostridium difficile

Shan, Jinyu; Patel, K.V.; Hickenbotham, Peter; Nale, Janet Y.; Hargreaves, Katherine R.; Clokie, Martha R. J.

doi:10.1128/aem.01311-12

Cited by 56 publications

(81 citation statements)

References 53 publications

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“…difficile strains produce R-type bacteriocins. After exposure to mitomycin C, many strains of C. difficile have been found by electron microscopy to produce particles with phage tail-like morphology (9,27,32) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile

et al. 2012

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c Clostridium difficile causes one of the leading nosocomial infections in developed countries, and therapeutic choices are limited. Some strains of C. difficile produce phage tail-like particles upon induction of the SOS response. These particles have bactericidal activity against other C. difficile strains and can therefore be classified as bacteriocins, similar to the R-type pyocins of Pseudomonas aeruginosa. These R-type bacteriocin particles, which have been purified from different strains, each have a different C. difficile-killing spectrum, with no one bacteriocin killing all C. difficile isolates tested. We have identified the genetic locus of these "diffocins" (open reading frames 1359 to 1376) and have found them to be common among the species. The entire diffocin genetic locus of more than 20 kb was cloned and expressed in Bacillus subtilis, and this resulted in production of bactericidal particles. One of the interesting features of these particles is a very large structural protein of ϳ200 kDa, the product of gene 1374. This large protein determines the killing spectrum of the particles and is likely the receptor-binding protein. Diffocins may provide an alternate bactericidal agent to prevent or treat infections and to decolonize individuals who are asymptomatic carriers.

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Section: Resultsmentioning

confidence: 99%

Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile

et al. 2012

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“…We were able to further propagate them to high titers and characterize them by TEM, PFGE, restriction profiling, and host range analysis. Although several prophages have been induced from clinical and environmental C. difficile isolates (17)(18)(19)(20)(21), there is a dearth of genomic and functional data on this group of phages and one main reason for that is the lack of suitable propagating hosts and conditions, which are essential for further characterization. It is also worth mentioning that, to our knowledge, strictly lytic (i.e., virulent) phages in- …”

Section: Discussionmentioning

confidence: 99%

“…Several putative prophages can be identified by bioinformatic analyses of C. difficile whole-genome sequences available in public repositories. Several prophages and phage tail-like particles have also been induced from C. difficile lysogens by using UV, mitomycin C, and other antibiotics, and some of these phages have been partially characterized by electron microscopy, PFGE, and restriction profiling (17)(18)(19)(20)(21)(22). Most phages are members of the Myoviridae family, i.e., phages with nonflexible and contractile tails, whereas very few are members of the Siphoviridae family, i.e., phages with long, flexible, and noncontractile tails (23).…”

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confidence: 99%

Characterization of Temperate Phages Infecting Clostridium difficile Isolates of Human and Animal Origins

Sekulović

Garneau

Néron

et al. 2014

Appl Environ Microbiol

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Clostridium difficile is a Gram-positive pathogen infecting humans and animals. Recent studies suggest that animals could represent potential reservoirs of C. difficile that could then transfer to humans. Temperate phages contribute to the evolution of most bacteria, for example, by promoting the transduction of virulence, fitness, and antibiotic resistance genes. In C. difficile, little is known about their role, mainly because suitable propagating hosts and conditions are lacking. Here we report the isolation, propagation, and preliminary characterization of nine temperate phages from animal and human C. difficile isolates. Prophages were induced by UV light from 58 C. difficile isolates of animal and human origins. Using soft agar overlays with 27 different C. difficile test strains, we isolated and further propagated nine temperate phages: two from horse isolates (CD481-1 and CD481-2), three from dog isolates (CD505, CD506, and CD508), and four from human isolates (CD24-2, CD111, CD146, and CD526). Two phages are members of the Siphoviridae family (CD111 and CD146), while the others are Myoviridae phages. Pulsed-field gel electrophoresis and restriction enzyme analyses showed that all of the phages had unique double-stranded DNA genomes of 30 to 60 kb. Phages induced from human C. difficile isolates, especially the members of the Siphoviridae family, had a broader host range than phages from animal C. difficile isolates. Nevertheless, most of the phages could infect both human and animal strains. Phage transduction of antibiotic resistance was recently reported in C. difficile. Our findings therefore call for further investigation of the potential risk of transduction between animal and human C. difficile isolates.

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“…Prophages reported in C. difficile so far belong to the Myoviridae or Siphoviridae family, although myoviruses tend to dominate (Hargreaves et al, 2013;Shan et al, 2012). There has been some evidence that prophages are involved in regulation of toxin production, possibly via quorum sensing loci (Goh, 2005;Sekulovic et al, 2011), but they do not carry virulence genes.…”

Section: Accepted Manuscript 12 or Antibiotic Resistamentioning

confidence: 99%

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

Elliott

Androga

Knight

et al. 2017

Infection, Genetics and Evolution

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Over the recent decades, Clostridium difficile infection (CDI) has emerged as a global public health threat. Despite growing attention, C. difficile remains a poorly understood pathogen, however, the exquisite sensitivity offered by next generation sequencing (NGS) technology has enabled analysis of the genome of C. difficile, giving us access to massive genomic data on factors such as virulence, evolution, and genetic relatedness within C. difficile groups. NGS has also demonstrated excellence in investigations of outbreaks and disease transmission, in both small and large-scale applications. This review summarizes the molecular epidemiology, evolution, and phylogeny of C. difficile, one of the most important pathogens worldwide in the current antibiotic resistance era.

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Prophage Carriage and Diversity within Clinically Relevant Strains of Clostridium difficile

Cited by 56 publications

References 53 publications

Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile

Novel High-Molecular-Weight, R-Type Bacteriocins of Clostridium difficile

Characterization of Temperate Phages Infecting Clostridium difficile Isolates of Human and Animal Origins

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

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