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bioRxiv · 10.1101/2024.08.27.609937

Plasmid-borne mcr-1 and Replicative Transposition of Episomal and Chromosomal blaNDM-1, blaOXA-69, and blaOXA-23 Carbapenemases in a Clinical Acinetobacter baumannii Isolate

Mmatli, M.·Mbelle, N. M.·Osei Sekyere, J.
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Abstract

BackgroundA multidrug-resistant clinical A. baumannii isolate with resistance to most antibiotics was isolated from a patient at an intensive care unit. The genetic environment, transcriptome, mobile, and resistome were characterized. MethodThe MicroScan system, disc diffusion, and broth microdilution were used to determine the resistance profile of the isolate. A multiplex PCR assay was also used to screen for carbapenemases and mcr-1 to -5 resistance genes. Efflux-pump inhibitors were used to evaluate efflux activity. The resistome, mobilome, epigenome, and transcriptome were characterized. Results & conclusionThere was phenotypic resistance to 22 of the 25 antibiotics tested, intermediate resistance to levofloxacin and nalidixic acid, and susceptibility to tigecycline, which corresponded to the 27 resistance genes found in the genome, most of which occurred in multiple copies through replicative transposition. A plasmid-borne (pR-B2.MM_C3) mcr-1 and chromosomal blaPER-7, blaOXA-69, blaOXA-23 (three copies), blaADC-25, blaTEM-1B, and blaNDM-1 were found within composite transposons, ISs, and/or class 1 and 2 integrons on genomic islands. Types I and II methylases and restriction endonucleases were in close synteny to these resistance genes within the genomic islands; chromosomal genomic islands aligned with known plasmids. There was a closer evolutionary relationship between the strain and global strains but not local or regional strains; the resistomes also differed. Significantly expressed/repressed genes (6.2%) included resistance genes, hypothetical proteins, mobile elements, methyltransferases, transcription factors, membrane and efflux proteins. The genomic evolution observed in this strain explains its adaptability and pandrug resistance and shows its genomic plasticity on exposure to antibiotics.

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Mmatli, M., Mbelle, N. M., Osei Sekyere, J.. 2024-08-27. Plasmid-borne mcr-1 and Replicative Transposition of Episomal and Chromosomal blaNDM-1, blaOXA-69, and blaOXA-23 Carbapenemases in a Clinical Acinetobacter baumannii Isolate. https://doi.org/10.1101/2024.08.27.609937

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