Abstract
Antibiotic resistance is a major concern in Clostridium difficile, the causative agent of antibiotic-associated diarrhea. Reduced susceptibility to first- and second-line agents is widespread, therefore various attempts have been made to seek alternative preventive and therapeutic strategies against this pathogen. In this work, the antimicrobial properties of asiatic acid were evaluated against C. difficile. Asiatic acid displayed substantial inhibitory effects on 19 C. difficile isolates collected from different sources with minimal inhibitory concentrations ranging from 10 to 20 μg/ml. Time kill analysis and minimal bactericidal concentration revealed potential bactericidal activity of this compound. Asiatic acid induced membrane damages and alterations in morphological ultrastructure in C. difficile, thereby causing the leakage of intracellular substances. Moreover, asiatic acid also displayed an inhibitory effect on cell motility, but did not interfere with biofilm formation and spore germination. Analysis of drug combination showed no synergistic effect between asiatic acid and vancomycin/metronidazole. Altogether, asiatic acid exhibited strong antimicrobial activity against vegetative cells and could serve as an alternative resource for tackling C. difficile.
Highlights
Clostridium difficile infection (CDI) is considered as a major leading cause of infectious diarrhea among hospitalized patients
An inhibitory effect of Asiatic acid (AA) on 19 C. difficile strains isolated from different sources was investigated by determining the Minimal inhibitory concentrations (MICs) values
AA exhibited substantial inhibitory effect against C. difficile strains with the MIC value of 10.0 μg/ml, excepted for human isolates 630 and RA156, whose MIC
Summary
Clostridium difficile infection (CDI) is considered as a major leading cause of infectious diarrhea among hospitalized patients. As a consequence of long-term antibiotic use, normal gastrointestinal biota is disrupted, allowing scarce population of C. difficile to overgrow and colonize in the gastrointestinal tract. The pathogenicity of C. difficile depends mostly on the toxins A and B. Both toxins induce the disruption of tight junctions of colonic epithelial cells, causing various symptoms ranging from mild diarrhea to severe pseudomembranous colitis (Voth and Ballard, 2005; Kuehne et al, 2010). Vancomycin and metronidazole are normally prescribed for the patients with CDI according to the clinical guideline, 25% of the cases continue to suffer from recurrence. Significant reduction in the susceptibility of C. difficile against
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