Epidemic Clostridium difficile Strains Demonstrate Increased Competitive Fitness Compared to Nonepidemic Isolates

Abstract

Clostridium difficile infection is the most common cause of severe cases of antibiotic-associated diarrhea (AAD) and is a significant health burden. Recent increases in the rate of C. difficile infection have paralleled the emergence of a specific phylogenetic clade of C. difficile strains (ribotype 027; North American pulsed-field electrophoresis 1 [NAP1]; restriction endonuclease analysis [REA] group BI). Initial reports indicated that ribotype 027 strains were associated with increased morbidity and mortality and might be hypervirulent. Although subsequent work has raised some doubt as to whether ribotype 027 strains are hypervirulent, the strains are considered epidemic isolates that have caused severe outbreaks across the globe. We hypothesized that one factor that could lead to the increased prevalence of ribotype 027 strains would be if these strains had increased competitive fitness compared to strains of other ribotypes. We developed a moderate-throughput in vitro model of C. difficile infection and used it to test competition between four ribotype 027 clinical isolates and clinical isolates of four other ribotypes (001, 002, 014, and 053). We found that ribotype 027 strains outcompeted the strains of other ribotypes. A similar competitive advantage was observed when two ribotype pairs were competed in a mouse model of C. difficile infection. Based upon these results, we conclude that one possible mechanism through which ribotype 027 strains have caused outbreaks worldwide is their increased ability to compete in the presence of a complex microbiota.

Antibiotic susceptibility and resistance profiles of Romanian Clostridioides difficile isolates

“…Previous reports [33] suggested that the lack of correspondence between in vitro and in vivo antibiotic activity may be explained by pharmacokinetic properties for MTR -high upper gastrointestinal absorption leading to low concentration in the intestine [35] -or physiological characteristics ensuring survival of the strains. Recent in vivo studies demonstrated the competitive advantage of PR 027 over other ribotypes, the authors suggesting an increased potential of PR 027 strains in using limited environmental resources [36]. Re-colonization of the patient through contact with spore-contaminated surfaces could be another cause of relapse.…”

Dietary trehalose enhances virulence of epidemic Clostridium difficile

“…10 To investigate potential mechanisms for increased fitness, we examined carbon source utilization in an epidemic RT027 isolate (CD2015) using the Biolog 96-well Phenotype MicroArray carbon source plates (see Methods and Extended Data Table 1). Out of several carbon sources identified that supported CD2015 growth, we found the disaccharide trehalose increased the growth yield of CD2015 by approximately 5-fold compared to a non-RT027 strain.…”

Clostridium difficile Infection in Production Animals and Avian Species: A Review

“…However, a study conducted by Robinson et al (2014) did not find a difference in the sporulation capacity between hypervirulent and nonhypervirulent strains. The thymidine synthase gene in RT 027 strains could confer a growth advantage for its competitive fitness (Robinson et al, 2014), however, the majority of factors that enhance fitness among epidemic strains of C. difficile are unknown.…”

“…Although still controversial, some studies have shown that epidemic strains of C. difficile have a higher sporulation capacity than nonepidemic strains and may persist in the environment longer (Merrigan et al, 2010). However, a study conducted by Robinson et al (2014) did not find a difference in the sporulation capacity between hypervirulent and nonhypervirulent strains. The thymidine synthase gene in RT 027 strains could confer a growth advantage for its competitive fitness (Robinson et al, 2014), however, the majority of factors that enhance fitness among epidemic strains of C. difficile are unknown.…”