Inhibitory effect of fidaxomicin on biofilm formation in Clostridioides difficile

• Published in: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy Vol. 26; no. 7; pp. 685 - 692
• Main Authors: Hamada, Masakaze, Yamaguchi, Tetsuo, Ishii, Yoshikazu, Chono, Koji, Tateda, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.07.2020
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Biofilm; Biofilms - drug effects; Clostridioides difficile; Clostridioides difficile - drug effects; Clostridioides difficile - genetics; Clostridium Infections - drug therapy; Clostridium Infections - microbiology; Fidaxomicin; Fidaxomicin - pharmacology; Fidaxomicin - therapeutic use; Flagellin - genetics; Gene Expression Regulation, Bacterial - drug effects; Humans; Microbial Sensitivity Tests; RNA, Bacterial - biosynthesis; RNA, Bacterial - isolation & purification; RNA, Messenger - biosynthesis; RNA, Messenger - isolation & purification; Transcription, Genetic - drug effects; Vancomycin; BHI; VAN; CV; DMSO; Biofilm; MNZ; Clostridioides difficile; Fidaxomicin; CDI; Vancomycin; FDX; CRM
• ISSN: 1341-321X; 1437-7780
• DOI: 10.1016/j.jiac.2020.02.014

Clostridioides difficile infection results from a disturbance of the normal microbial flora of the colon, allowing proliferation of C. difficile and toxin production by toxigenic strains. Fidaxomicin, a macrocyclic antibiotic that prevents RNA synthesis in C. difficile and inhibits spore formation, toxin production, and cell proliferation, is clinically effective in treating C. difficile infection. As recent studies have suggested that biofilm formation influences C. difficile colonization and infection in the colon, we undertook the present study to determine the effects of fidaxomicin on C. difficile biofilm formation. Sub-minimum inhibitory concentrations (MICs) of fidaxomicin inhibited biofilm formation by C. difficile UK027 and delayed planktonic growth. Sub-MICs of vancomycin did not inhibit biofilm formation or affect planktonic growth. In C. difficile UK027 exposed to sub-MICs of fidaxomicin, mRNA expression of biofilm-related flagellin gene fliC was slightly increased compared with that of other biofilm-related genes (pilA1, cwp84, luxS, dccA, and spo0A). In conclusion, this study indicates that sub-MICs of fidaxomicin inhibit C. difficile UK027 biofilm formation by influencing cell growth and fliC transcription.