Abstract
BackgroundCarbapenems are the antibiotics of choice to treat infections caused by Acinetobacter baumannii, and resistance to this class can be determined by loss of membrane permeability and enzymatic mechanisms. Here, we analyzed the basis of carbapenem resistance in clinical A. baumannii isolates from different Brazilian regions.ResultsThe analyses addressed the carbapenemase activity of OXA-23, CarO expression and alterations in its primary structure. Susceptibility test revealed that the strains presented the COS (Colistin-Only-Sensitive) profile. PCR and sequencing showed the presence of the chromosomally-encoded blaOXA-51 in all isolates. The majority of strains (53%) carried the carbapenemase blaOXA-23 gene associated with ISAba1. The Hodge test indicated that these strains are carbapenemase producers. PFGE revealed 14 genotypes among strains from Rio de Janeiro and Maranhão. The influence of carO on imipenem resistance was evaluated considering two aspects: the composition of the primary amino acid sequence; and the expression level of this porin. Sequencing and in silico analyses showed the occurrence of CarOa, CarOb and undefined CarO types, and Real Time RT-PCR revealed basal and reduced carO transcription levels among isolates.ConclusionsWe concluded that, in general, for these Brazilian isolates, the major carbapenem resistance mechanism was due to OXA-23 carbapenemase activity and that loss of CarO porin plays a minor role in this phenotype. However, it was possible to associate the carO alleles and their expression with imipenem resistance. Therefore, these findings underline the complexity in addressing the role of different mechanisms in carbapenem resistance and highlight the possible influence of CarO type in this phenotype.
Highlights
Carbapenems are the antibiotics of choice to treat infections caused by Acinetobacter baumannii, and resistance to this class can be determined by loss of membrane permeability and enzymatic mechanisms
Acinetobacter baumannii has been considered one of the major nosocomial pathogens worldwide, and it is included in the group of ESKAPE bugs, in which some lineages effectively escape the action of antibacterial drugs [1]
The high imipenem resistance (MIC, ≥ 32 μg/mL) presented in all strains harbouring blaOXA-23 can be due to its overexpression driven by the ISAba1 promoter [4]
Summary
Carbapenems are the antibiotics of choice to treat infections caused by Acinetobacter baumannii, and resistance to this class can be determined by loss of membrane permeability and enzymatic mechanisms. Carbapenems remain the antibiotic of choice to treat A. baumannii and other Gram-negative infections due to both a wider spectrum of antibacterial activity and less frequent side effects Their overuse and misuse have selected for nosocomial isolates presenting association with ISAba, is spread in A. baumannii worldwide, and it is the most prevalent OXA allele in isolates from Brazil [3,5,6,7]. The 25/29 kDa heat-modifiable carbapenem-associated outer membrane protein (CarO) is a porin with a β-barrel topology This channel allows the selective uptake of amino acids and imipenem (but not meropenem) due to its structural conformation and to the presence of an imipenem binding site [8,9]. Concerning the participation of CarO porin in the resistance phenotype, few descriptive studies have only shown the presence/absence of the gene and protein, resulting in a lack of studies showing the association of the carO alleles and their expression with the resistance phenotype
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