Combined in silico approach and whole genome sequencing: Acinetobacter baumannii ST218 isolate harboring ADC-73 β-lactamase which has a similar C-loop with ADC-56 and ADC-68 β-lactamase

Abstract

PurposeMultidrug-resistant Acinetobacter baumannii is a noteworthy nosocomial-pathogen and these pathogen-borne infections are difficult to treat. It is significant to make strain typing with WGS and to add new genome data to the literature. Therefore, in our study, we aimed to strain typing of the A. baumannii (A24) isolated from Turkey and reveal informations about ADC-73 β-lactamase. MethodsVITEK 2 system was used for the determination of antibiotic susceptibility. WGS was done on the Illumina NovaSeq 6000 platform. WGS results were analyzed with VFDB, ResFinder, PubMLST, IS Finder. Web-based bioinformatics software, homology modelling, molecular docking and dynamics simulations were used to determine all structural information about ADC-73 β-lactamase. ResultsA24 was found to be multidrug-resistant. Various virulence factors were found in A24. The sequence type of the isolate was determined as ST218. Genes encoding β-lactamase and aminoglycoside modifying enzymes, and IS elements were present in the genome of A24. Besides, secondary and 3D structures of ADC-73 were analyzed. Following, cefepime and imipenem were docked to ADC-56, ADC-68, and ADC-73 and interactions and stability of substrates were simulated. The binding-energies of imipenem to ADC-68 and ADC-73 were calculated −9.44 and −5.98 kcal/mol, respectively. Likewise, binding-energies of cefepime to ADC-56 and ADC-73 were calculated as −19.84 and −36.54 kcal/mol. ConclusionA. baumannii ST218 isolate containing ADC-73 was reported for the first time in Turkey by WGS, and the effect of G225S mutation in this β-lactamase on conformational change and possible interactions with cefepime and impinem were investigated in silico.