Discovery of a novel natural product inhibitor of Clostridioides difficile with potent activity in vitro and in vivo.

ABSTRACT: Clostridioides difficile infection is a global health threat and remains the primary cause of hospital-acquired infections worldwide. The burgeoning incidence and severity of infections coupled with high rates of recurrence have created an urgent need for novel therapeutics. Here, we report a novel natural product scaffold as a potential anticlostridial lead with antivirulence properties and potent activity both in vitro and in vivo. A whole cell phenotypic screening of 1,000 purified natural products identified 6 compounds with potent activity against C. difficile (minimum inhibitory concentration (MIC) range from 0.03 to 2 μg/ml). All these 6 compounds were non-toxic to human colorectal cells. The natural product compounds also inhibited the production of key toxins, TcdA and TcdB, the k

SUBMITTER: Pal R 

PROVIDER: S-EPMC9359557 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature