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Title: Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile
Authors: Matthew Phanchana
Tanaporn Phetruen
Phurt Harnvoravongchai
Ponlawoot Raksat
Puey Ounjai
Surang Chankhamhaengdecha
Tavan Janvilisri
Mahidol University
Keywords: Multidisciplinary
Issue Date: 1-Dec-2020
Citation: Scientific Reports. Vol.10, No.1 (2020)
Abstract: © 2020, The Author(s). Drug resistance in Clostridioides difficile becomes a public health concern worldwide, especially as the hypervirulent strains show decreased susceptibility to the first-line antibiotics for C. difficile treatment. Therefore, the simultaneous discovery and development of new compounds to fight this pathogen are urgently needed. In order to determinate new drugs active against C. difficile, we identified ticagrelor, utilized for the prevention of thrombotic events, as exhibiting potent growth-inhibitory activity against C. difficile. Whole-cell growth inhibition assays were performed and compared to vancomycin and metronidazole, followed by determining time-kill kinetics against C. difficile. Activities against biofilm formation and spore germination were also evaluated. Leakage analyses and electron microscopy were applied to confirm the disruption of membrane structure. Finally, ticagrelor’s ability to synergize with vancomycin and metronidazole was determined using checkerboard assays. Our data showed that ticagrelor exerted activity with a MIC range of 20–40 µg/mL against C. difficile. This compound also exhibited an inhibitory effect on biofilm formation and spore germination. Additionally, ticagrelor did not interact with vancomycin nor metronidazole. Our findings revealed for the first time that ticagrelor could be further developed as a new antimicrobial agent for fighting against C. difficile.
ISSN: 20452322
Appears in Collections:Scopus 2020

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