Co‐evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase‐encoding plasmid during carbapenem exposure

Abstract

OXA-23 is the predominant carbapenemase in carbapenem-resistant Acinetobacter baumannii. The co-evolutionary dynamics of A. baumannii and OXA-23-encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a bla OXA−23 -containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a subinhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of bla OXA−23 in pAZJ221, interfering allele dynamics, and chromosomal locus-level parallelism were observed. To characterize genotype-to-phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3′ → 5′) GMP-metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of bla OXA−23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of bla OXA−23 increased host

High Genetic Diversity of Carbapenem-Resistant Acinetobacter baumannii Isolates Recovered in Nigerian Hospitals in 2016 to 2020

“…One interesting observation was the presence of two copies of the bla OXA-23 gene in the oxf ST1114/1841 and oxf ST231 strains. A previous study by Zhang and colleagues reported the duplication of a plasmid-borne bla OXA-23 gene in an A. baumannii strain in the presence of subinhibitory concentrations of carbapenem ( 46 ). This duplication was reported to confer improved fitness in carbapenem-containing media but was also associated with a fitness cost in antibiotic-free media.…”

High genetic diversity andblaNDM-1prevalence amongAcinetobacter baumanniiin Nigerian hospitals

“…One interesting observation was the presence of two copies of the bla OXA-23 gene in the ST1114/1841 and ST231 strains. A previous study by Zhang and colleagues reported the duplication of a plasmid-borne bla OXA-23 gene in an A. baumannii strain in the presence of sub-inhibitory concentrations of carbapenem 63 . This duplication was reported to confer improved fitness in carbapenem-containing media but was also associated with a fitness cost in antibiotic-free media.…”

Gram-Negative ESKAPE Bacteria Surveillance in COVID-19 Pandemic Exposes High-Risk Sequence Types of Acinetobacter baumannii MDR in a Tertiary Care Hospital

“…Interestingly, statistically significant changes in resistance to β-lactam antibiotics (ampicillin/sulbactam), aminoglycosides (amikacin and gentamicin), carbapenems (meropenem and imipenem) and a folate metabolism inhibitor (trimethoprim/sulfamethoxazole) were observed in this member. These resistances are typically conferred by the presence of mobile genetic elements, where conjugative plasmids carrying genes coding for carbapenemases play an important role in the dissemination of carbapenem resistance [50][51][52].…”