Variations in Virulence and Molecular Biology among Emerging Strains of Clostridium difficile

Abstract

SUMMARY Clostridium difficile is a Gram-positive, spore-forming organism which infects and colonizes the large intestine, produces potent toxins, triggers inflammation, and causes significant systemic complications. Treating C. difficile infection (CDI) has always been difficult, because the disease is both caused and resolved by antibiotic treatment. For three and a half decades, C. difficile has presented a treatment challenge to clinicians, and the situation took a turn for the worse about 10 years ago. An increase in epidemic outbreaks related to CDI was first noticed around 2003, and these outbreaks correlated with a sudden increase in the mortality rate of this illness. Further studies discovered that these changes in CDI epidemiology were associated with the rapid emergence of hypervirulent strains of C. difficile , now collectively referred to as NAP1/BI/027 strains. The discovery of new epidemic strains of C. difficile has provided a unique opportunity for retrospective and prospective studies that have sought to understand how these strains have essentially replaced more historical strains as a major cause of CDI. Moreover, detailed studies on the pathogenesis of NAP1/BI/027 strains are leading to new hypotheses on how this emerging strain causes severe disease and is more commonly associated with epidemics. In this review, we provide an overview of CDI, discuss critical mechanisms of C. difficile virulence, and explain how differences in virulence-associated factors between historical and newly emerging strains might explain the hypervirulence exhibited by this pathogen during the past decade.

ProbioticSaccharomyces boulardiiCNCM I-745 prevents outbreak-associatedClostridium difficile-associated cecal inflammation in hamsters

“…However, most of the experimental work examining the effects of S.b in CDI models has been limited to nonoutbreak-associated C. difficile strains, mostly with strain VPI10463. However, the increased incidence and severity of the CDI global outbreaks has been associated with the emergence of outbreak-associated strains (20). The exact mechanism of the hypervirulence of these emerging strains is not fully understood (20).…”

“…Live, but not heated, S. boulardii significantly inhibited outbreak-associated C. difficile strain-mediated cecal inflammation in hamsters. The incidence and severity of C. difficile outbreaks have been increasing with the emergence of outbreak-associated strains (20). We next infected hamsters with C. difficile strains ribotype 017, 027, 078, previously associated with several outbreaks (51), using the experimental protocol described in Fig.…”

“…However, the increased incidence and severity of the CDI global outbreaks has been associated with the emergence of outbreak-associated strains (20). The exact mechanism of the hypervirulence of these emerging strains is not fully understood (20). Moreover, studies with the use of probiotics in emerging CDI at both the preclinical and clinical levels have been limited.…”

Clostridium difficile PCR Ribotype 018, a Successful Epidemic Genotype

“…These epidemiological changes coincided with the emergence and epidemic spread of C. difficile strains belonging to the PCR ribotype (RT) 027/North American pulsedfield gel electrophoresis type 1 (NAP1) (6). Indeed, RT027 became the predominant strain in many geographical regions, as documented in different epidemiological studies, and, since 2005, several countries have conducted epidemiological surveillance to monitor its spread (7,8). It has been reported to occur in at least 38 U.S. states and in 16 European countries, being also responsible for outbreaks (7, 9).…”

Microbiological aspects of Clostridium difficile infection in Italy: results of a study performed in 2012-2013

“…Infatti, si è osservato non solo un aumento dell'incidenza delle infezioni ma anche della loro gravità, delle recidive e della mortalità. La causa è da ricercare nell'emergenza e nella diffusione di ceppi particolarmente virulenti, detti ipervirulenti (3,10). In particolare, i ceppi appartenenti al PCR- ribotype 027 (conosciuto anche come pulse-field-type NAP1, restriction endonuclease analysis group B1) si sono diffusi nel mondo a partire dall'inizio degli anni 2000 causando infezioni gravi e epidemie (4,6).…”