Affiliation:
1. Department of Life Sciences and Systems Biology, University of Torino, Turin, Italy
2. Department of Molecular Biotechnology and Health, University of Torino, Turin, Italy
Abstract
ABSTRACT
Antimicrobial resistance is a global issue currently resulting in the deaths of hundreds of thousands of people a year worldwide. Data present in the literature illustrate the emergence of many bacterial species that display resistance to known antibiotics;
Acinetobacter
spp. are a good example of this. We report here that
Acinetobacter radioresistens
has a Baeyer-Villiger monooxygenase (Ar-BVMO) with 100% amino acid sequence identity to the ethionamide monooxygenase of multidrug-resistant (MDR)
Acinetobacter baumannii
. Both enzymes are only distantly phylogenetically related to other canonical bacterial BVMO proteins. Ar-BVMO not only is capable of oxidizing two anticancer drugs metabolized by human FMO3, danusertib and tozasertib, but also can oxidize other synthetic drugs, such as imipenem. The latter is a member of the carbapenems, a clinically important antibiotic family used in the treatment of MDR bacterial infections. Susceptibility tests performed by the Kirby-Bauer disk diffusion method demonstrate that imipenem-sensitive
Escherichia coli
BL21 cells overexpressing Ar-BVMO become resistant to this antibiotic. An agar disk diffusion assay proved that when imipenem reacts with Ar-BVMO, it loses its antibiotic property. Moreover, an NADPH consumption assay with the purified Ar-BVMO demonstrates that this antibiotic is indeed a substrate, and its product is identified by liquid chromatography-mass spectrometry to be a Baeyer-Villiger (BV) oxidation product of the carbonyl moiety of the β-lactam ring. This is the first report of an antibiotic-inactivating BVMO enzyme that, while mediating its usual BV oxidation, also operates by an unprecedented mechanism of carbapenem resistance.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference57 articles.
1. Schreckenberger PC, Daneshvar MI, Hollis DG. 2007. Acinetobacter, Achromobacter, Chryseobacterium, Moraxella, and other nonfermentative Gram-negative rods, p 770–802. In Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA (ed), Manual of clinical microbiology, 9th ed. ASM Press, Washington, DC.
2. Towner K. 2006. The genus Acinetobacter, p 746–758. In Dworkin M (ed), The prokaryotes. Springer, New York, NY.
3. Acinetobacter spp. as nosocomial pathogens: microbiological, clinical, and epidemiological features
4. Distribution of Acinetobacter species on human skin: comparison of phenotypic and genotypic identification methods
5. Microbiological characteristics of sepsis in a University hospital
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