In-depth genetic analysis of<i>Clostridium</i><i>difficile</i>PCR-ribotype 027 strains reveals high genome fluidity including point mutations and inversions

Stabler, Richard A.; Valiente, Esmeralda; Dawson, Lisa F.; He, Miao; Parkhill, Julian; Wren, Brendan W.

doi:10.4161/gmic.1.4.11870

Cited by 30 publications

(39 citation statements)

References 16 publications

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“…The term lysogney refers to the ability of a host cell and the virus to enter a latent stage where they grow together and virus is functionally hidden in the genome as prophages giving little or no detriment to the bacterial host. All C. difficile bacteriophages characterized so far are lysogenic in nature [15, 17, 22-25] and DNA sequences of C. difficile strains also revealed prophages as part of the highly mosaic genomes where nearly 11% is made of mobile genetic elements [26-28] indicating the co-evolution of C. difficile phages with its host. In the genus Clostridium , several toxin-encoding genes are located on nonintegrative lysogenic phages and lysogenic phages [29, 30].…”

Section: Discussionmentioning

confidence: 99%

In vivo lysogenization of a Clostridium difficile bacteriophage ФCD119

2011

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Clostridium difficile is a nosocomial pathogen identified as the cause of antibiotic associated diarrhea and colitis. In this study, we have documented the lysogeny of a C. difficile bacteriophage in hamsters during C. difficile infection. The lysogens isolated from the hamsters were toxin typed and their phage integration site was confirmed by PCR. Through toxin ELISA it was found that the toxin production in the in vivo isolated lysogens was affected due to ΦCD119 lysogenization as in the case of in vitro isolated ΦCD119 lysogens. Together our findings indicate that a baceriophage can lysogenize its C. difficile host even during the infection process and highlights the importance of lysogeny of C. difficile phages as an evolutionary adaptation for survival.

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Section: Discussionmentioning

confidence: 99%

In vivo lysogenization of a Clostridium difficile bacteriophage ФCD119

2011

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“…C. difficile has a highly dynamic and mosaic genome comprising a high proportion (ϳ11% in strain 630) of mobile genetic elements. These include bacteriophages, group I introns, insertion sequences (IS), sigK intervening (skin) elements, clustered regularly interspersed short palindromic repeat (CRISPR)-cas elements, genomic islands, and transposable and conjugative elements, accompanied by an extensive range of accessory genes (52,53,55,58,59).…”

Section: Difficile Phylogenomics and Strain Diversitymentioning

confidence: 99%

“…Those authors looked for the presence of these genetic markers in a larger set of C. difficile RT027 genomes and found that many were acquired very recently, potentially explaining the genetic basis for the emergence of RT027 and its successful dissemination (56). In addition to the acquisition of new genes, numerous point mutations and nucleotide inversions have been identified within or upstream of putative coding regions in epidemic strains of RT027, which likely result in changes in gene functionality and phenotype (59).…”

Section: The Complex and Dynamic Epidemiology Of CDI Evolutionary Hismentioning

confidence: 99%

Diversity and Evolution in the Genome of Clostridium difficile

et al. 2015

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SUMMARY Clostridium difficile infection (CDI) is the leading cause of antimicrobial and health care-associated diarrhea in humans, presenting a significant burden to global health care systems. In the last 2 decades, PCR- and sequence-based techniques, particularly whole-genome sequencing (WGS), have significantly furthered our knowledge of the genetic diversity, evolution, epidemiology, and pathogenicity of this once enigmatic pathogen. C. difficile is taxonomically distinct from many other well-known clostridia, with a diverse population structure comprising hundreds of strain types spread across at least 6 phylogenetic clades. The C. difficile species is defined by a large diverse pangenome with extreme levels of evolutionary plasticity that has been shaped over long time periods by gene flux and recombination, often between divergent lineages. These evolutionary events are in response to environmental and anthropogenic activities and have led to the rapid emergence and worldwide dissemination of virulent clonal lineages. Moreover, genome analysis of large clinically relevant data sets has improved our understanding of CDI outbreaks, transmission, and recurrence. The epidemiology of CDI has changed dramatically over the last 15 years, and CDI may have a foodborne or zoonotic etiology. The WGS era promises to continue to redefine our view of this significant pathogen.

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“…1D). Although C. difficile strain VPI 10463 has been widely studied and is commonly used in mouse models of C. difficile colitis (4, 9, 17, 21), we wanted to confirm the importance of MyD88 in defense against the disease by using another toxin-producing strain of C. difficile, CD196 (25). As shown in Fig.…”

Section: Myd88mentioning

confidence: 99%

Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis

et al. 2012

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Clostridium difficile can infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. Little is known about the innate immune signaling pathways that marshal inflammatory responses to C. difficile infection and whether protective and pathogenic inflammatory responses can be dissociated. Toll-like receptors predominantly signal via the MyD88 adaptor protein and are important mediators of innate immune signaling in the intestinal mucosa. Here, we demonstrate that MyD88-mediated signals trigger neutrophil and CCR2-dependent Ly6C hi monocyte recruitment to the colonic lamina propria (cLP) during infection, which prevent dissemination of bystander bacteria to deeper tissues. Mortality is markedly increased in MyD88-deficient mice following C. difficile infection, as are parameters of mucosal tissue damage and inflammation. Antibody-mediated depletion of neutrophils markedly increases mortality, while attenuated recruitment of Ly6C hi monocytes in CCR2-deficient mice does not alter the course of C. difficile infection. Expression of CXCL1, a neutrophilrecruiting chemokine, is impaired in the cLP of MyD88 ؊/؊ mice. Our studies suggest that MyD88-mediated signals promote neutrophil recruitment by inducing expression of CXCL1, thereby providing critical early defense against C. difficile-mediated colitis.

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In-depth genetic analysis ofClostridiumdifficilePCR-ribotype 027 strains reveals high genome fluidity including point mutations and inversions

Cited by 30 publications

References 16 publications

In vivo lysogenization of a Clostridium difficile bacteriophage ФCD119

In vivo lysogenization of a Clostridium difficile bacteriophage ФCD119

Diversity and Evolution in the Genome of Clostridium difficile

Critical Role for MyD88-Mediated Neutrophil Recruitment during Clostridium difficile Colitis

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