Phenotypic comparison of Clostridium dificile RT017 strains with other toxigenic strains

Abstract

Clostridium difficile causes nosocomial infection worldwide especially in the patients with long-term usage of broad spectrum antibiotics Clinical symptoms of C difficile infections may present as diarrhea and pseudomembranous colitis (PMN) Therefore controlling of C difficile infection (CDI) is the most important public-health issues In the United States and Europe RT027 was known to be the epidemic and hypertoxigenic clone However the different epidemiologic trends in ribotype strain were observed in other continents In Asia RT017 is the predominant typeable ribotype in toxigenic strains the prevalence rate is around 10% in Asia Many studies demonstrated that the severity of CDI caused by RT 017 is similar to that caused by RT027 Compared to RT027 RT017 encodes only one toxin gene tcdB In a CDC surveillance program 1 112 C difficile isolates were collected from five hospitals from 2015 to 2016 in Taiwan In this study 842 (75 8%) strains were toxin-producing strains and 270 (24 2%) were non-toxigenic strains where the proportion of RT017 in toxigenic strains was approximately 9 97% However it is unclear whether the RT017 strains cause severe diseases Here we evaluated the virulence of RT017 strain in vivo and found RT017 strain induced more severe disease symptoms than CD630 (RT012) did but as well as a clinical UK epidemic C difficile strain R20291 (RT027) did By in vitro testing both tcdB expression and toxin glucosyltransferase activity were not as high as R20291 Compared to R20291 biofilm formation in RT017 strains was similar to that in R20291 the aggregation ability in RT017 was stronger spore formation rate of RT017 was similar to R20291 In addition C difficile produces small molecule autoinducer-2 (AI-2) which can influence gene expression such as virulence luminescence and biofilm formation across different species The levels of AI-2 that induces bioluminescence in Vibrio harveyi MM32 were measured The AI-2 levels in RT017 spent medium is similar to that in R20291 Using spent medium of a less virulent strain (CD630) the spore formation was increased Finally used C elegans as a model to examine the toxicity of spent medium the survival rate was decreased when treating worms with spent medium of RT017 which cannot be reversed by heating the spent medium Taken together RT017 has higher virulence in vivo ability in formation of spore and higher AI-2 production which might contribute to the disease progression

Date of Award	2018 Aug 28
Original language	English
Supervisor	Pei-Jane Tsai (Supervisor)