Clinical variants of the native class d beta-lactamase of acinetobacter baumannii pose an emerging threat through ıncreased hydrolytic activity against carbapenems

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dc.contributor.authorSchroder, Emma C.
dc.contributor.authorKlamer, Zachary L.
dc.contributor.authorSaral, Ayşegül
dc.contributor.authorSugg, Kyle A.
dc.contributor.authorJune, Cynthia M.
dc.contributor.authorWymore, Troy
dc.contributor.authorSzarecka, Agnieszka
dc.contributor.authorLeonard, David A.
dc.date.accessioned2020-05-28T11:30:41Z
dc.date.available2020-05-28T11:30:41Z
dc.date.issued2016
dc.departmentAÇÜ, Rektörlüken_US
dc.description.abstractThe threat posed by the chromosomally encoded class D beta-lactamase of Acinetobacter baumannii (OXA-51/66) has been unclear, in part because of its relatively low affinity and turnover rate for carbapenems. Several hundred clinical variants of OXA51/66 have been reported, many with substitutions of active-site residues. We determined the kinetic properties of OXA-66 and five clinical variants with respect to a wide variety of beta-lactam substrates. The five variants displayed enhanced activity against carbapenems and in some cases against penicillins, late-generation cephalosporins, and the monobactam aztreonam. Molecular dynamics simulations show that in OXA-66, P130 inhibits the side-chain rotation of I129 and thereby prevents doripenem binding because of steric clash. A single amino acid substitution at this position (P130Q) in the variant OXA-109 greatly enhances the mobility of both I129 and a key active-site tryptophan (W222), thereby facilitating carbapenem binding. This expansion of substrate specificity represents a very worrisome development for the efficacy of beta-lactams against this troublesome pathogen.
dc.description.sponsorshipHHS \ NIH \ National Institute of Allergy and Infectious Diseases (NIAID):1R15AI082416 National Science Foundation (NSF): CNS-1228291en_US
dc.identifier.citationSchroder, E. C., Klamer, Z. L., Saral, A., Sugg, K. A., June, C. M., Wymore, T., ... & Leonard, D. A. (2016). Clinical variants of the native class D β-lactamase of Acinetobacter baumannii pose an emerging threat through increased hydrolytic activity against carbapenems. Antimicrobial agents and chemotherapy, 60(10), 6155-6164, doi.10.1128/AAC.01277-16.en_US
dc.identifier.doi10.1128/AAC.01277-16
dc.identifier.endpage6164en_US
dc.identifier.issue10en_US
dc.identifier.scopusqualityQ1
dc.identifier.startpage6155en_US
dc.identifier.urihttps://hdl.handle.net/11494/2079
dc.identifier.volume60en_US
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorSaral, Ayşegül
dc.language.isoenen_US
dc.publisherAmer Soc Microbiologyen_US
dc.relation.ispartofAntimicrobial Agents and Chemotherapy
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keywords Available]en_US
dc.titleClinical variants of the native class d beta-lactamase of acinetobacter baumannii pose an emerging threat through ıncreased hydrolytic activity against carbapenemsen_US
dc.typeArticle

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