Abstract
Clostridium difficile is a Gram-positive, spore-forming anaerobic human gastrointestinal pathogen. C. difficile infection (CDI) is a major health concern worldwide, with symptoms ranging from diarrhea to pseudomembranous colitis, toxic megacolon, sepsis, and death. CDI onset and progression are mostly caused by intestinal dysbiosis and exposure to C. difficile spores. Current treatment strategies include antibiotics; however, antibiotic use is often associated with high recurrence rates and an increased risk of antibiotic resistance. Medium-chain fatty acids (MCFAs) have been revealed to inhibit the growth of multiple human bacterial pathogens. Components of coconut oil, which include lauric acid, have been revealed to inhibit C. difficile growth in vitro. In this study, we demonstrated that lauric acid exhibits potent antimicrobial activities against multiple toxigenic C. difficile isolates in vitro. The inhibitory effect of lauric acid is partly due to reactive oxygen species (ROS) generation and cell membrane damage. The administration of lauric acid considerably reduced biofilm formation and preformed biofilms in a dose-dependent manner. Importantly, in a mouse infection model, lauric acid pretreatment reduced CDI symptoms and proinflammatory cytokine production. Our combined results suggest that the naturally occurring MCFA lauric acid is a novel C. difficile inhibitor and is useful in the development of an alternative or adjunctive treatment for CDI.
Highlights
Clostridium difficile is a Gram-positive, spore-forming bacillus that was first isolated from the gut of an infant and became medically important when it was found to be the leading cause of antibioticassociated diarrhea (AAD) in hospital settings worldwide (Smits et al, 2016)
To identify the free fatty acids (FAs) with potent C. difficile inhibitory effects, FAs C3–C16 were coincubated with log-phase-grown C. difficile cells, and their Minimum Bactericidal Concentration (MBC) were determined (Table 2)
In recent years, the ability of C. difficile to tolerate multiple commonly prescribed antibiotics, its production of potent cytotoxins, and its high recurrence rate have resulted in C. difficile infection (CDI) becoming a healthcare concern worldwide (Martin et al, 2016)
Summary
Clostridium difficile is a Gram-positive, spore-forming bacillus that was first isolated from the gut of an infant and became medically important when it was found to be the leading cause of antibioticassociated diarrhea (AAD) in hospital settings worldwide (Smits et al, 2016). The principal virulence factors of C. difficile are two large cytotoxins, toxin A and toxin B, which have been reported to exhibit enterotoxigenic and cytotoxic activity (Pruitt et al, 2010; Abt et al, 2016). Both toxins are capable of severely inflaming the colon and disrupting the epithelial mucosal surface. The recently Food and Drug Administration (FDA)-approved antibiotic fidaxomycin has been identified as having similar treatment effects as those of vancomycin while having a reduced impact on the gut flora (Louie et al, 2012), the recurrence rate is still high. Alternative treatment and preventive strategies against CDI are required
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