Screening of Natural Products and Approved Oncology Drug Libraries for Activity against Clostridioides difficile

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dc.contributor.authorPal, Rushaen
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:11:16Zen
dc.date.available2020-09-21T16:11:16Zen
dc.date.issued2020-04-06en
dc.date.updated2020-09-21T16:11:14Zen
dc.description.abstractClostridioides difficile is the most common cause of healthcare-associated diarrhea. Infection of the gastrointestinal tract with this Gram-positive, obligate anaerobe can lead to potentially life-threatening conditions in the antibiotic-treated populace. New therapeutics are urgently needed to treat this infection and prevent its recurrence. Here, we screened two libraries from the National Cancer Institute, namely, the natural product set III library (117 compounds) and the approved oncology drugs set V library (114 compounds), against C. difficile. In the two libraries screened, 17 compounds from the natural product set III library and 7 compounds from the approved oncology drugs set V library were found to exhibit anticlostridial activity. The most potent FDA-approved drugs (mitomycin C and mithramycin A) and a promising natural product (aureomycin) were further screened against 20 clinical isolates of C. difficile. The anticancer drugs, mitomycin C (MIC50 = 0.25 μg/ml) and mithramycin A (MIC50 = 0.015 μg/ml), and the naturally derived tetracycline derivative, aureomycin (MIC50 = 0.06 μg/ml), exhibited potent activity against C. difficile strains. Mithramycin A and aureomycin were further found to inhibit toxin production by this pathogen. Given their efficacy, these compounds can provide a quick supplement to current treatment to address the unmet needs in treating C. difficile infection and preventing its recurrence.en
dc.description.versionPublished versionen
dc.format.extent8 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 5966 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-020-63029-0en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-020-63029-0 (PII)en
dc.identifier.pmid32249833 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100022en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectTOXIN-Ben
dc.subjectINFECTIONen
dc.subjectEPIDEMIOLOGYen
dc.subjectVIRULENCEen
dc.subjectMETRONIDAZOLEen
dc.subjectFIDAXOMICINen
dc.subjectINHIBITIONen
dc.subjectVANCOMYCINen
dc.subjectMICROBIOTAen
dc.subjectMECHANISMen
dc.titleScreening of Natural Products and Approved Oncology Drug Libraries for Activity against Clostridioides difficileen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-03-24en
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
pubs.organisational-group/Virginia Techen

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