dc.creator | de Belder, Denise Gisele | |
dc.creator | Ghiglione, Barbara | |
dc.creator | Pasteran, Fernando | |
dc.creator | de Mendieta, Juan Manuel | |
dc.creator | Corso, Alejandra | |
dc.creator | Curto, Lucrecia María | |
dc.creator | Di Bella, Adriana | |
dc.creator | Gutkind, Gabriel Osvaldo | |
dc.creator | Gómez, Sonia Alejandra | |
dc.creator | Power, Pablo | |
dc.date.accessioned | 2021-03-16T14:11:02Z | |
dc.date.accessioned | 2022-10-14T22:53:12Z | |
dc.date.available | 2021-03-16T14:11:02Z | |
dc.date.available | 2022-10-14T22:53:12Z | |
dc.date.created | 2021-03-16T14:11:02Z | |
dc.date.issued | 2020-11 | |
dc.identifier | de Belder, Denise Gisele; Ghiglione, Barbara; Pasteran, Fernando; de Mendieta, Juan Manuel; Corso, Alejandra; et al.; Comparative Kinetic Analysis of OXA-438 with Related OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamases; American Chemical Society; ACS Infectious Diseases; 6; 11; 11-2020; 3026-3033 | |
dc.identifier | 2373-8227 | |
dc.identifier | http://hdl.handle.net/11336/128373 | |
dc.identifier | 2373-8227 | |
dc.identifier | CONICET Digital | |
dc.identifier | CONICET | |
dc.identifier.uri | https://repositorioslatinoamericanos.uchile.cl/handle/2250/4316240 | |
dc.description.abstract | Novel variants of OXA-48-type enzymes with the ability to hydrolyze oxyimino-cephalosporins and carbapenems are increasingly reported. Since its first report in 2011, OXA-163 is now extensively spread throughout Argentina, and several variants like OXA-247 have emerged. Here, we characterized a new blaOXA-48-like variant, OXA-438, and we performed a comparative kinetic analysis with the local variants OXA-247 and OXA-163 and the internationally disseminated OXA-48. blaOXA-163, blaOXA-247, and blaOXA-438 were located in a 70 kb IncN2 conjugative plasmid. OXA-438 presented mutations in the vicinity of conserved KTG (214-216), with a 2-aa deletion (R220-I221) and a D224E shift (as in OXA-163) compared to OXA-48. Despite Kpn163 (OXA-163), Kpn247 (OXA-247) and Eco438 (OXA-438) were resistant to meropenem and ertapenem, and the transconjugants (TC) remained susceptible (however, the carbapenems minimum inhibitory concentrations were ≥3 times 2-fold dilutions higher than the acceptor strain). TC163 and Eco48 were resistant to oxyimino-cephalosporins, unlike TC247 and TC438. kcat/Km values for cefotaxime in OXA-163 were slightly higher than the rest of the variants that were accompanied by a lower Km for carbapenems. For OXA-163, OXA-247, and OXA-438, the addition of NaHCO3 improved kcat values for both cefotaxime and ceftazidime; carbapenems kcat/Km values were higher than for oxyimino-cephalosporins. Mutations occurring near the conserved KTG in OXA-247 and OXA-438 are probably responsible for the improved carbapenems hydrolysis and decreased inactivation of oxyimino-cephalosporins compared to OXA-163. Dichroism results suggest that deletions at the β5-β6 loop seem to impact the structural stability of OXA-48 variants. Finally, additional mechanisms are probably involved in the resistance pattern observed in the clinical isolates. | |
dc.language | eng | |
dc.publisher | American Chemical Society | |
dc.relation | info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/acsinfecdis.0c00537 | |
dc.relation | info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acsinfecdis.0c00537 | |
dc.rights | https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ | |
dc.rights | info:eu-repo/semantics/openAccess | |
dc.subject | CARBAPENEMASES | |
dc.subject | OXA-163 | |
dc.subject | OXYIMINO-CEPHALOSPORINS | |
dc.subject | SODIUM BICARBONATE | |
dc.subject | Β5−Β6 LOOP | |
dc.title | Comparative Kinetic Analysis of OXA-438 with Related OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamases | |
dc.type | info:eu-repo/semantics/article | |
dc.type | info:ar-repo/semantics/artículo | |
dc.type | info:eu-repo/semantics/publishedVersion | |