Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages

Cairns, M. D.; Preston, Mark D.; Hall, Christopher D.; Gerding, Dale N.; Hawkey, Peter M.; Kato, Hiroo; Kim, H.; Kuijper, Ed J.; Lawley, Trevor D.; Pituch, Hanna; Reid, Sharon J.; Kullin, Brian; Riley, Thomas V.; Solomon, Katie; Tsai, Pei-Jane; Weese, J. Scott; Stabler, Richard A.; Wren, Brendan W.

doi:10.1128/jcm.01296-16

Cited by 52 publications

(42 citation statements)

References 68 publications

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“…Many nontoxigenic strains of C. difficile, together with RT 017, are placed in clade 4 of the five main phylogenetic clades of C. difficile (24). Given the high prevalence of both nontoxigenic and RT 017 strains in this study, and others in Thailand (11) and Indonesia (12), it is likely that clade 4 of C. difficile has evolved in the Asian region in contrast to a recent report suggesting that RT 017 C. difficile evolved in North America (25). However, little is known about the prevalence of nontoxigenic strains in other regions of the world, with a publication bias toward toxigenic strains because they cause infection.…”

Section: Discussioncontrasting

confidence: 61%

High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia

et al. 2018

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Accumulating evidence shows a high prevalence of in Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigated infection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates of characterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.

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Section: Discussioncontrasting

confidence: 61%

High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia

et al. 2018

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“…Coupled with many previous reports of RT 017 [6,17,38] and recent reports of RT 369 [18,19] in Asian countries, it appears that A−B+ strains are endemic to the region and a recent review of RT 017 concluded that the global spread of this MLST Clade 4 lineage member is a relatively recent event [4]. However, these findings contradict an earlier study of Cairns et al [39] who used phylogeographic analyses to suggest a North American origin for RT 017.…”

Section: Discussionmentioning

confidence: 88%

Clostridioides difficile infection in the Asia-Pacific region

Collins

Sohn

et al. 2019

Emerging Microbes & Infections

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Clostridioides difficile causes healthcare-related diarrhoea in high-income countries. Highly resistant spores persist in healthcare facilities, primarily infecting patients who have recently received antimicrobials. C. difficile infection (CDI) has been studied in detail in North America and Europe; however, the epidemiology of CDI elsewhere, including the Asia-Pacific region, is largely unknown. A survey of CDI was performed in 13 Asia-Pacific countries. Epidemiological data on 600 cases were collected and molecular typing undertaken on 414 C. difficile isolates. Healthcare facilityassociated CDI comprised 53.6% of cases, while community-associated CDI was 16.5%. The median age of cases was 63.0 years and 45.3% were female, 77.5% had used antibiotics in the previous 8 weeks, most frequently thirdgeneration cephalosporins (31.7%), and 47.3% had used proton pump inhibitors. Recurrence (9.1%) and mortality (5.2%) rates were low, while complications including colitis or pseudomembranous colitis (13.8%), colectomy (0.4%), and toxic megacolon (0.2%) were uncommon. Common C. difficile strains were ribotypes 017 (16.7%), 014/020 (11.1%) and 018 (9.9%), with wide variation between countries. Binary toxin-positive strains of C. difficile were detected rarely. Overall, disease severity appeared mild, and mortality and recurrence were low. Continued education about, and surveillance of, CDI in Asia are required to reduce the burden of disease.

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“…Toxinotypes are therefore important from clinical, diagnostic, research and development perspectives. However, so far, only a few toxinotype representatives have been included in comparative genomic studies, performed either for epidemiological purposes [14][15][16][17] or for understanding virulence [18][19][20]. In addition, the evolution of the PaLoc was previously investigated with respect to the known population structure of the species, but in these reports not all known PaLoc variants, as defined by toxinotype, were included [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution

et al. 2020

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Clostridioides difficile is a common cause of nosocomial diarrhoea. Toxins TcdA and TcdB are considered to be the main virulence factors and are encoded by the PaLoc region, while the binary toxin encoded in the CdtLoc region also contributes to pathogenicity. Variant toxinotypes reflect the genetic diversity of a key toxin-encoding 19 kb genetic element (the PaLoc). Here, we present analysis of a comprehensive collection of all known major C. difficile toxinotypes to address the evolutionary relationships of the toxin gene variants, the mechanisms underlying the origin and development of variability in toxin genes and the PaLoc, and the relationship between structure and function in TcdB variants. The structure of both toxin genes is modular, composed of interspersed blocks of sequences corresponding to functional domains and having different evolutionary histories, as shown by the distribution of mutations along the toxin genes and by incongruences of domain phylogenies compared to overall C. difficile cluster organization. In TcdB protein, four mutation patterns could be differentiated, which correlated very well with the type of TcdB cytopathic effect (CPE) on cultured cells. Mapping these mutations to the three-dimensional structure of the TcdB showed that the majority of the variation occurs in surface residues and that point mutation at residue 449 in alpha helix 16 differentiated strains with different types of CPE. In contrast to the PaLoc, phylogenetic trees of the CdtLoc were more consistent with the core genome phylogenies, but there were clues that CdtLoc can also be exchanged between strains.

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Comparative Genome Analysis and Global Phylogeny of the Toxin Variant Clostridium difficile PCR Ribotype 017 Reveals the Evolution of Two Independent Sublineages

Cited by 52 publications

References 68 publications

High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia

High Prevalence of Toxigenic and Nontoxigenic Clostridium difficile Strains in Malaysia

Clostridioides difficile infection in the Asia-Pacific region

Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution

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