Biological characteristics associated with virulence in Clostridioides difficile ribotype 002 in Hong Kong

Abstract

Clostridioides difficile infection (CDI) is a common cause of nosocomial diarrhea and can sometimes lead to pseudomembranous colitis and toxic megacolon. We previously reported that the PCR ribotype 002 was a common C. difficile ribotype in Hong Kong that was associated with increased mortality. In this study, we assessed in vitro bacteriological characteristics and in vivo virulence of ribotype 002 compared to other common ribotypes, including ribotypes 012, 014 and 046. We observed significantly higher toxin A (p < 0.05) and toxin B (p < 0.05) production, sporulation (p < 0.001) and germination rates (p < 0.0001) in ribotype 002 than other common ribotypes. In a murine model of C. difficile infection, ribotype 002 caused significantly more weight loss (p < 0.001) and histological damage (p < 0.001) than other common ribotypes. These findings may have contributed to the higher prevalence and mortality observed, and provided mechanistic insights that can help public surveillance and develop novel therapeutics to combat against this infection.

Systematic review on the definition and predictors of severe Clostridiodes difficile infection

“…Table 1 details the 31 papers included in the study 9‐36 . Of the 31 papers, the majority were from the USA (11 studies) or Europe (nine studies), only two from Asia (Japan and Korea), two from Mexico, one from Israel and one from Canada.…”

“…49,50 Other strains such as ribotype 002 has been associated with antibiotic resistance and higher mortality, 51 and its in vivo virulence has been demonstrated as compared with other common ribotypes. 52 The evidence on this is conflicting, with other sources stating that specific ribotypes do not predict severe infection when adjusted for the influence of other variables, and focus should be placed on patient rather than pathogen characteristics. 53 Novel biomarkers for Clostridiodes difficile infection severity.…”

Genomic study of European Clostridioides difficile ribotype 002/sequence type 8

“…Overview of the C. difficile ST8/RT002 lineage C. difficile ST8/RT002 is prevalent worldwide [9,12,13,16,17,63,64] and can cause severe CDI [65,66]. This ST/RT has been shown to have a higher ability to cause clinically complicated infections compared to other RTs but has not provoked such severe disease as RT027 or RT078 [18]. As it is found in different animal species and environmental niches [67][68][69][70][71], a One Health approach is needed to understand the epidemiology and transmission routes of this clinically relevant RT lineage.…”

Trends in Incidence and Clinical Outcomes of Clostridioides difficile Infection, Hong Kong

“…This difference may also explain the decrease in the relative proportion of severe CDI. Furthermore, ribotypes 002 and 017 are both virulent strains with high antimicrobial resistance ( 8 , 10 , 12 ), which may have been positively selected in the past because of excessive antimicrobial drug use. Now that the use of antimicrobial drugs has been declining, these strains may have seen a decline in prevalence, which lowered mortality rates.…”

“…Other toxigenic strains, such as C . difficile ribotype 369, which was associated with multiple epidemics in Japan, have been reported in various Southeast Asia countries ( 9 ), whereas C. difficile ribotype 002 was reported to be common in Hong Kong, China, and was associated with increased virulence ( 10 , 11 ). Continuous surveillance, therefore, is important to prevent outbreaks of CDI.…”