Investigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeae

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dc.contributor.authorElkashif, Ahmeden
dc.contributor.authorSeleem, Mohamed N.en
dc.date.accessioned2020-09-21T16:14:41Zen
dc.date.available2020-09-21T16:14:41Zen
dc.date.issued2020-03-27en
dc.date.updated2020-09-21T16:14:39Zen
dc.description.abstractNeisseria gonorrhoeae represents an urgent public health threat due to the rapid emergence of resistance to current antibiotics and the limited number of anti-gonococcal agents currently in clinical trials. This study utilized a drug repositioning strategy to investigate FDA-approved gold-containing drugs against N. gonorrhoeae. Auranofin, sodium aurothiomalate and aurothioglucose inhibited 48 clinical isolates of N. gonorrhoeae including multidrug-resistant strains at a concentration as low as 0.03 µg/mL. A time-kill assay revealed that auranofin exhibited rapid bactericidal activity against N. gonorrhoeae. Moreover, both sodium aurothiomalate and aurothioglucose did not inhibit growth of vaginal protective commensal lactobacilli. Auranofin, in combination with azithromycin, ceftriaxone, cefixime or tetracycline showed an additive effect against four N. gonorrhoeae strains, suggesting the possibility of using auranofin in dual therapy. Moreover, auranofin reduced the burden of intracellular N. gonorrhoeae by over 99% outperforming the drug of choice ceftriaxone. Auranofin was found superior to ceftriaxone in reducing the secretion of the pro-inflammatory cytokine IL-8 by endocervical cells infected with N. gonorrhoeae. Furthermore, auranofin exhibited a prolonged post-antibiotic effect over 10 h, as well as inability to generate resistant mutants. Overall, the current study suggests that repurposing gold-containing drugs, like auranofin, for treatment of gonorrhea warrants further investigation.en
dc.description.versionPublished versionen
dc.format.extent9 page(s)en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 5602 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-020-62696-3en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other10.1038/s41598-020-62696-3 (PII)en
dc.identifier.pmid32221472 (pubmed)en
dc.identifier.urihttp://hdl.handle.net/10919/100033en
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.subjectGLOBAL QUALITY-ASSURANCEen
dc.subjectINHIBITIONen
dc.subjectMECHANISMSen
dc.subjectRIFAMPICINen
dc.subjectGUIDELINEen
dc.subjectMUTATIONSen
dc.subjectINFECTIONen
dc.subjectFREQUENCYen
dc.subjectDIAGNOSISen
dc.subjectCOSTen
dc.titleInvestigation of auranofin and gold-containing analogues antibacterial activity against multidrug-resistant Neisseria gonorrhoeaeen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-02-20en
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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