Insertion sequences and blaOXA-58 genes in the evolution of carbapenem resistance among clonally related Acinetobacter baumannii strains isolated in a Rosario hospital

PIAZZA AINELÉN; LIMANSKY ADRIANA S; VIALE A. M.; MUSSI MARÍA ALEJANDRA

Mar del Plata

Congreso; VIII Congreso de Microbiología General SAMIGE; 2012

Acinetobacter baumannii is a nosocomial opportunistic pathogen, now accounting for a large percentage of infections among immunocompromised inpatients. Insertion sequences (IS) constitute mobile elements modulating genome plasticity and evolution in bacteria. We identified previously ISAba825 and ISAba125 (interrupting the carO gene coding for an outer membrane channel) in carbapenem resistant A. baumannii clinical strains. We further evaluated whether other members of the Acinetobacter genus could constitute reservoirs for these mobile genetic elements. In 22 different species of the genus Acinetobacter ISAba125 showed a widespread distribution, whereas ISAba825 was restricted only to certain A. baumannii clonal groups. Among them, we also identified ISAba825 upstream of a blaOXA-58 gene in a carbapenem resistant strain, generating a hybrid promoter that significantly stimulated blaOXA-58 expression promoting a 64-128 fold increase in carbapenems MIC values. We evaluated here whether this constitutes a general mechanism leading to carbapenem resistance acquisition in A. baumannii. For this purpose, we analyzed the distribution of the ISAba825-blaOXA-58 arrangement in different carbapenem resistant strains obtained from hospitals of Rosario City, Santa Fe. We first identified blaOXA-58-harboring strains, and further analyzed the presence of ISAba825-blaOXA-58 by PCR. We found this arrangement only in a group of clonally related strains, in which two relevant subgroups were identified. Subgroup 1 was represented by carbapenem resistant strains harbouring a plasmid-borne ISAba825-blaOXA-58 arrangement. Subgroup 2 was conformed by strains showing intermediate resistance to carbapenems, and contained the blaOXA-58 gene in a plasmid and ISAba825 in the chromosome. The clonal group also included carbapenem sensitive strains in which both blaOXA-58 and ISAba825 were absent. These results prompted us to propose that antibiotic pressure in the hospital could have selected carbapenem resistant strains among this clonal group in which the hybrid promoter generated by the insertion of ISAba825 lead to blaOXA-58 overexpression. This work thus contributes to the understanding of the role of horizontal gene transfer and mobile elements in the evolution of A. baumannii resistant strains in clinical settings.