In vitro and in vivo activities of the carbonic anhydrase inhibitor, dorzolamide, against vancomycin-resistant enterococci

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dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorElhassanny, Ahmed E. M.en
dc.contributor.authorFlaherty, Daniel P.en
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-08-25T11:56:38Zen
dc.date.available2021-08-25T11:56:38Zen
dc.date.issued2021-03-30en
dc.date.updated2021-08-25T11:56:36Zen
dc.description.abstractVancomycin-resistant enterococci (VRE) are a serious public health threat and a leading cause of healthcare-associated infections. Bacterial resistance to antibiotics recommended for the treatment of enterococcal infections complicates the management of these infections. Hence, there is a critical need for the discovery of new anti-VRE agents. We previously reported carbonic anhydrase inhibitors (CAIs) as new potent VRE inhibitors. In the present study, the activity of the CAI, dorzolamide was evaluated against VRE both in vitro and in vivo. Dorzolamide exhibited potent activity against a panel of clinical VRE isolates, with minimum inhibitory concentration (MIC) values ranging from 1 µg/mL to 8 µg/mL. A killing kinetics experiment determined that dorzolamide exhibited a bacteriostatic effect against VRE, which was similar to the drug of choice (linezolid). Dorzolamide interacted synergistically with gentamicin against four strains of VRE, and exhibited an additive interaction with gentamicin against six VRE strains, reducing gentamicin’s MIC by several folds. Moreover, dorzolamide outperformed linezolid in an in vivo VRE colonization reduction mouse model. Dorzolamide significantly reduced the VRE burden in fecal samples of mice by 2.9-log10 (99.9%) and 3.86-log10 (99.99%) after 3 and 5 days of treatment, respectively. Furthermore, dorzolamide reduced the VRE count in the cecal (1.74-log10 (98.2%) reduction) and ileal contents (1.5-log10 (96.3%)) of mice, which was superior to linezolid. Collectively, these results indicate that dorzolamide represents a promising treatment option that warrants consideration as a supplement to current therapeutics used for VRE infections.en
dc.description.versionPublished versionen
dc.format.extent17 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e11059 (Article number)en
dc.identifier.doihttps://doi.org/10.7717/peerj.11059en
dc.identifier.eissn2167-8359en
dc.identifier.issn2167-8359en
dc.identifier.orcidSeleem, Mohamed [0000-0003-0939-0458]en
dc.identifier.other11059 (PII)en
dc.identifier.pmid33850651en
dc.identifier.urihttp://hdl.handle.net/10919/104700en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherPeerJen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000635097000004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCarbonic anhydrase inhibitorsen
dc.subjectVancomycin-resistant enterococci (VRE)en
dc.subjectAntibiotics resistanceen
dc.subjectVRE decolonizing agentsen
dc.subjectAntibiotics resistanceen
dc.subjectCarbonic anhydrase inhibitorsen
dc.subjectVRE decolonizing agentsen
dc.subjectVancomycin-resistant enterococci (VRE)en
dc.subject06 Biological Sciencesen
dc.subject11 Medical and Health Sciencesen
dc.titleIn vitro and in vivo activities of the carbonic anhydrase inhibitor, dorzolamide, against vancomycin-resistant enterococcien
dc.title.serialPeerJen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2021-02-12en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
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/CVM T&R Facultyen

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