title: Plasmid borne Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) and AdeABC efflux pump conferring carbapenem-tigecycline resistance among Acinetobacter baumannii isolates harboring TnAbaRs.
abstract: Here we studied the prevalence and mechanisms of simultaneous resistance to carbapenem and tigecycline and accumulation of resistance determinants reservoirs in genome of Acinetobacter baumannii (A. baumannii) clinical isolates. Susceptibility of the isolates were measured to 18 antimicrobial agents. Genetic diversity of the microbial population was determined using the International Clonal lineage typing (IC typing), multiple locus VNTR analysis (MLVA) and plasmid profiling methods. To detect the AbaRs, Carbapenem-Hydrolyzing Class D β-Lactamases (CHDLs) genes, AdeABC efflux pump genes and resistance determinants, PCR was used. Filter mating experiments were used to prove that if carbapenem resistance genes are located on conjugative plasmids or not. Among the A. baumannii clinical isolates, 40.8% were carbapenem-tigecycline resistant and in this population, 46.9% were belonging to IC I, IC II or IC III and 53.1% were IC variants. These isolates had fallen in 40 MLVA types and were harboring plasmids in multiple numbers and sizes. In this study, blaOXA-23-likewas the most prevalent CHDL and conjugation analysis proved that the carbapenem resistance genes are located on conjugative plasmids. All efflux pump genes, except for adeC, were detected in all carbapenem-tigecycline resistant A. baumannii (CTRAb) isolates. Resistance determinants were distributed in both TnAbaRs and R plasmids with a shift toward the R plasmids. Emerging of carbapenem resistant A. baumannii (CRAB) with simultaneous resistance to the last line therapy including tigecycline represent emerging of extensively drug resistance (XDR) and pandrug resistance (PDR) phenotypes that would be a great threat to our public health system.
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Savari
authors.affiliation: Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ekrami
authors.affiliation: Infectious and Tropical Disease Research Center, Hormozgan University of Medical Sciences, Bandar-Abbas, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shoja
authors.affiliation: Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran; Laser Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: abahador@sina.tums.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Bahador
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001692:Biological Transport; D015780:Carbapenems / Q000378:metabolism*; D003227:Conjugation, Genetic; D014644:Genetic Variation; D005838:Genotype; D006868:Hydrolysis; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000378:metabolism; D058889:Molecular Typing; D010957:Plasmids / Q000032:analysis*; D000078304:Tigecycline; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D026901:Membrane Transport Proteins; D000078304:Tigecycline; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline
keywords: Acinetobacter baumannii; Antibiotic resistance; Carbapenems; Tigecycline