期刊
MICROBIAL DRUG RESISTANCE
卷 28, 期 8, 页码 849-852出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/mdr.2021.0405
关键词
oxacillinases; carbapenem resistance; hydrolysis
资金
- Coordenacao de Aperfeicoamento de Pessoal de Ni'vel Superior (CAPES)
- National Council for Science and Technological Development (CNPq) [312066/2019-8]
Pseudomonas aeruginosa is often associated with life-threatening infections due to its intrinsic and acquired antimicrobial mechanisms, including different types of beta-lactamases. The study found that OXA-488 has a higher catalytic efficiency for benzylpenicillin and imipenem compared to OXA-50, although its carbapenemase activity is considered weak. Additionally, OXA-488 and OXA-494 have increased affinity for penicillins, contributing to improved catalytic efficiency against ampicillin.
Pseudomonas aeruginosa is an opportunist pathogen usually associated with life threatening infections and exhibits a set of intrinsic and acquired antimicrobial mechanisms. Although resistance to penicillins-like compounds is commonly associated with the chromosomal Pseudomonas-derived cephalosporinases beta-lactamase, the real contribution of OXA-50, a second chromosomally encoded beta-lactamase, remains unclear. In this study, we characterized the biochemical properties of OXA-50, OXA-488, and OXA-494. Both oxacilinases differ from OXA-50 in two amino acids each. The bla(OXA-50), bla(OXA-488), and bla(OXA-494) were cloned into pET26b(+) that was transformed into Escherichia coli DH5 alpha strain, expressed in E. coli BL21 strain, and then purified for obtaining the hydrolytic parameters. Benzylpenicillin was the preferential substrate instead of oxacillin. Besides, OXA-488 showed a threefold increase in catalytic efficiency for benzylpenicillin, and it was twofold more efficient in hydrolyzing imipenem, compared with OXA-50, although such carbapenemase activity was considered weak. In addition, OXA-488 and OXA-494 showed an increased affinity for penicillins, which contributed to the increased catalytic efficiency against ampicillin, especially OXA-488. Chromosomally encoded resistance mechanisms are usually overshadowed by acquired mechanisms. However, understanding their real contribution is essential to comprehend the versatile profiles verified in P. aeruginosa isolates. Such information can help to choose the best therapy in a scenario of limited options.
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