Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus

Monot, Marc; Eckert, Catherine; Lemire, Astrid; Hamiot, Audrey; Dubois, Thomas; Tessier, Claude; Dumoulard, Bruno; Hamel, Benjamin; Petit, A; Lalande, V.; Ma, Laurence; Bouchier, Christiane; Barbut, Frédéric; Dupuy, Bruno

doi:10.1038/srep15023

Cited by 126 publications

(149 citation statements)

References 52 publications

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“…Nevertheless, the ability of the latter assay to identify the mutations that result in moxifloxacin resistance may be useful in future surveillance studies. A further benefit of the Hain test is that it targets all the known toxin genes and, therefore, has a greater chance of detecting variant strains, such as the A + B 2 strain recently isolated in France, which cannot be detected using the GeneXpert method (Monot et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre

Rajabally

Kullin

Ebrahim

et al. 2016

Journal of Medical Microbiology

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Accurate diagnosis of Clostridium difficile infection is essential for disease management.A clinical and molecular analysis of C. difficile isolated from symptomatic patients at Groote Schuur Hospital, South Africa, was conducted to establish the most suitable clinical test for the diagnosis and characterization of locally prevalent strains. C. difficile was detected in stool samples using enzyme-based immunoassays (EIA) and nucleic acid amplification methods, and their performance was compared with that of C. difficile isolation using direct selective culture combined with specific PCR to detect the C. difficile tpi gene, toxin A and B genes and binary toxin genes. Toxigenic isolates were characterized further by ribotyping. Selective culture isolated 32 C. difficile strains from 145 patients (22 %). Of these, the most prevalent (50 %) were of ribotype 017 (toxin A 2 B + ) while 15.6 % were ribotype 001 (toxin A + B + ). No ribotype 027 strains or binary toxin genes (cdtA and cdtB) were detected. The test sensitivities and specificities, respectively, of four commercial clinical diagnostic methods were as follows: ImmunoCard Toxins A & B (40 % and 99.1 %), VIDAS C. difficile Toxin A & B (50 % and 99.1 %), GenoType CDiff (86.7 % and 88.3 %) and Xpert C. difficile (90 % and 97.3 %). Ribotype 001 and 017 strains had a 100 % detection rate by Xpert C. difficile, 100 % and 93.3 % by GenoType CDiff, 75 % and 53.3 % by ImmunoCard and 75 % and 60 % by VIDAS, respectively. The overall poor performance of EIA suggests that a change to PCR-based testing would assist diagnosis and ensure reliable detection of locally prevalent C. difficile 017 strains. INTRODUCTIONOver the last decade, Clostridium difficile infection (CDI) has emerged as an important healthcare problem, both in the hospital setting and in the community. There has been growing concern over its rising incidence, disease severity and mortality. Major epidemics, causing significant loss of lives, have been reported in North America and Europe (Birgand et al., 2010; Healthcare Commission, 2006; Pépin et al., 2004). These epidemics have been attributed to virulent strains capable of producing more than ten times the amount of toxins than conventional strains (Kelly & LaMont, 2008;McDonald et al., 2005;O'Connor et al., 2009). In addition, the 'hyper virulent' 027 strain has developed resistance to antibiotics such as fluoroquinolones (Pépin et al., 2005).In South Africa, information on CDI remains scarce. Yet, there are some studies that have shown that CDI in this Abbreviations: CA, community acquired; CDI, Clostridium difficile infection; EIA, enzyme-based immunoassays; GDH, glutamate dehydrogenase; HA, hospital acquired; NLR, negative likelihood ratio; NPV, negative predictive value; PLR, positive likelihood ratio; PPV, positive predictive value. part of the world is not insignificant. In 2008, an institution in Pretoria reported a sudden increase in toxin-producing C. difficile, raising the alert of a possible outbreak and sensitizing its clinicians (Lekala...

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Section: Discussionmentioning

confidence: 99%

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre

Rajabally

Kullin

Ebrahim

et al. 2016

Journal of Medical Microbiology

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“…A partial form of the CdtLoc (4.2 kb) containing an intact cdtR alongside fragments of cdtA and cdtB is common within clade 1, but does not occur in the other binary toxin-negative PaLoc-positive clade, clade 4 (Geric Stare et al, 2007). The presence of an intact CdtLoc is associated with changes in the PaLoc, and these occur in clades 2, 3 and 5, as well as in clade C-I (Monot et al, 2015). Interestingly, CdtR has been shown to regulate the production of toxins A and B, but only in some strains (Lyon et al, 2016).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Strains producing just toxin A have only described relatively recently and carry an unusual monotoxin locus consisting of toxin A and the holin UviB instead of tcdE, found elsewhere in the genome than at the PaLoc integration site (Monot et al, 2015). In toxinotype XXXII strains, which belong to clade C-II, a variant version of the PaLoc lacking tcdA and tcdC is also found at an alternative location in the genome (Janezic et al, 2015b).…”

Section: Other Lct Elementsmentioning

confidence: 99%

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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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“…In most strains, the PaLoc is located at the same site in the chromosome 77,78 . The PaLoc in most pathogenic C. difficile strains encodes two large homologous toxins (TcdA and TcdB) and three proteins that seem to regulate toxin production and secretion (TcdR, TcdE and TcdC) 74,75,78 (FIG. 4a).…”

Section: The Large Clostridial Toxins Tcda and Tcdbmentioning

confidence: 99%

Clostridium difficile Infection

Wilcox¹,

Vehreschild²,

Nord³

2015

Annual Update in Intensive Care and Emergency Medicine

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Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis -the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota. Competing interests statement W.K.S. has performed research for Cubist. D.L. has performed research for Immuron and Adenium Biotech. D.B.L. has performed research for MedImmune and Merck. M.H.W. has received consulting fees from Abbott, Actelion Pharmaceuticals, Astellas, AstraZeneca, Bayer, Cerexa, Cubist, Durata, The European Tissue Symposium, The Medicines Company, MedImmune, Merck, Motif Biosciences, Nabriva, Optimer, Paratek, Pfizer, Roche, Sanofi Pasteur, Seres Therapeutics, Summit Pharmaceuticals, and Synthetic Biologics. M.H.W. has also received lecture fees from Abbott, Alere, Astellas, AstraZeneca, Pfizer and Hoffmann La Roche, and received grant support from Abbott, Actelion, Astellas, bioMérieux, Cubist, Da Volterra, The European Tissue Symposium, Merck and Summit Pharmaceuticals. E.J.K. has performed research for Cubist, Novartis and Qiagen, and has participated in advisory forums of Astellas, Optimer, Actelion, Pfizer, Sanofi Pasteur and Seres Therapeutics. These companies had no role in the writing of this Primer. HHS Public AccessAuthor manuscript Nat Rev Dis Primers. Author manuscript; available in PMC 2017 June 01. Published in final edited form as:Nat Rev Dis Primers. ; 2: 16020. doi:10.1038/nrdp.2016.20. Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptClostridium difficile is a Gram-positive obligate anaerobic bacterium that was originally identified as part of the flora of healthy infants in 1935, described as an "actively motile, heavy-bodied rod with elongated subterminal or nearly terminal spores" (REF. 1) (FIG. 1). At that time, the strain was named Bacillus difficilis to reflect the difficulty experienced in isolating and culturing it. De...

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Clostridium difficile: New Insights into the Evolution of the Pathogenicity Locus

Cited by 126 publications

References 52 publications

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

Clostridium difficile Infection

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