RT Journal Article
T1 Activity of the β-Lactamase inhibitor LN-1-255 against carbapenem-hydrolyzing class D β-lactamases from Acinetobacter baumannii
A1 Vázquez Ucha, Juan Carlos
A1 Maneiro Rey, María
A1 Martínez Guitián, Marta
A1 Buynak, John
A1 Bethel, Christopher R.
A1 Bonomo, Roberto A.
A1 Bou, Germán
A1 Poza Domínguez, Margarita
A1 González Bello, Concepción
A1 Beceiro Casas, Alejandro
AB The number of infections caused by Gram-negative pathogens carrying carbapenemases is increasing, and the group of carbapenem-hydrolyzing class D β-lactamases (CHDLs) is especially problematic. Several clinically important CHDLs have been identified in A. baumannii, including OXA-23, OXA-24/40, OXA-58, OXA-143, OXA-235, and the chromosomally encoded OXA-51. The selection and dissemination of carbapenem-resistant A. baumannii strains constitutes a serious global threat. Carbapenems have been successfully utilized as last resort antibiotics for the treatment of multi-drug-resistant A. baumannii infections. However, the spread of OXA carbapenemases is compromising the continued use of these antimicrobials. In response to this clinical issue, it is necessary and urgent to design and develop new specific inhibitors with efficacy against these enzymes. The aim of this work is to characterize the inhibitory activity of LN-1-255 (a 6-alkylidene-2-substituted penicillin sulfone) and compare it to that of two established inhibitors (avibactam and tazobactam) against the most relevant enzymes of each group of class D carbapenemases in A. baumannii. The β-lactamase inhibitor LN-1-255 demonstrated excellent microbiological synergy and inhibition kinetics parameters against all tested CHDLs, and a significantly higher activity than tazobactam and avibactam. A combination of carbapenems and LN-1-255 was effective against A. baumannii class D carbapenemases. Docking assays confirmed the affinity of LN-1-255 for the active site of these enzymes. LN-1-255 represents a potential new β-lactamase inhibitor, which may have a significant role in eradicating infections caused by A. baumannii isolates carrying CHDLs
PB American Society for Microbiology
SN 0066-4804
YR 2017
FD 2017
LK http://hdl.handle.net/10347/16923
UL http://hdl.handle.net/10347/16923
LA eng
NO Vázquez-Ucha, J., Maneiro, M., Martínez-Guitián, M., Buynak, J., Bethel, C., & Bonomo, R. et al. (2017). Activity of the β-Lactamase Inhibitor LN-1-255 against Carbapenem-Hydrolyzing Class D β-Lactamases from Acinetobacter baumannii. Antimicrobial Agents And Chemotherapy, 61(11), e01172-17. doi: 10.1128/aac.01172-17
NO This work was supported by the Spanish National Plans for Scientific Research, Development and Technological Innovation 2008-2011 and 2013-2016 and funded by the ISCIII- General Subdirection of Assessment and Promotion of the Research-European Regional Development Fund (ERDF) “A way of making Europe”:  PI12/00552 to G.B. and PI14/00059 to M.P. and A.B. Also, this study was supported in part by funds from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (USA) under award numbers R01AI063517 and R01AI100560, by funds and/or facilities provided by the Cleveland Department of Veterans Affairs, the Veterans Affairs Merit Review Program Award 1I01BX001974 and the Geriatric Research Education and Clinical Center VISN 10 to R.A.B., and by the Spanish Ministry of Economy and Competiveness (SAF2013-42899-R), Xunta de Galicia (GRC2013-041) and the European Regional Development Fund (ERDF) to C.GB. J.V. was financially supported by the Sara Borrell Programme ISCIII-FEDER (CD13/00373). J.V.H. and A.B. were financially supported by the Miguel Servet Programme ISCIII-FEDER (CP13/00226)
DS Minerva
RD 28 abr 2026