Objectives. The emergency of carbapenem-resistant Acinetobacter baumannii constitutes a worrisome problem worldwide. Aminoglycoside therapy is generally employed to treat carbapenem-resistant A. baumannii, but the rapid selection of aminoglycoside resista

CAMERANESI, M; MORAN-BARRIO, J.; LIMANSKY, A; REPIZO G; SALCEDO S; VIALE, A

Simposio; International Symposium on the Biology of Acinetobacter; 2015

Objectives. The emergency of carbapenem-resistant Acinetobacter baumannii constitutes a worrisome problem worldwide. Aminoglycoside therapy is generally employed to treat carbapenem-resistant A. baumannii, but the rapid selection of aminoglycoside resistant strains rapidly follows antibiotic therapy. We studied here the molecular causes of the combined resistances to these antibiotics and their possible dissemination mechanisms among the A. baumannii population in public health care institutions in Argentina. Methods. We analyzed two epidemiologically-related A. baumannii clinical strains assigned to ST104, Ab242 and Ab825, displaying resistance to both carbapenems and aminoglycosides. Plasmids bearing resistance determinants isolated from these bacteria were thoroughly characterized by cloning, sequencing and database searching, and their dissemination potential evaluated by their ability to confer resistance to sensitive A. baumannii strains. Results. Both Ab242 and Ab825 harboured a novel plasmid-borne genetic platform carrying a blaOXA-58 gene which is overexpressed due to an ISAba825 insertion into an upstream ISAba3-like element. araC and lysE genes are present downstream of the above arrangement, being the latter interrupted by a TnaphA6 composite transposon conferring aminoglycoside resistance. The TnaphA6 site of insertion differs from those already characterized in other A. baumannii plasmids, thus indicating separate origins between them. The whole platform, encompassing 9,588 bp, is bracketed by two short recombination sites and is contiguous to a recombinase gene thus encompassing all necessary resources for its mobilization into other sites either on the chromosome or plasmids. Noticeably, it was found in opposite orientations within a 25 kbp homologous region shared by plasmids carried by Ab242 and Ab825. Moreover, plasmids containing this arrangement were capable of forming concatemers with other plasmids present in these bacteria via short identical recombination sites. Conclusion. The plasmid-borne genetic platform described above and its associated recombinase gene probably represent an adaptability module carrying all required functions for self-dissemination by inversion mechanisms and/or concatenate formation. Evolution of these flexible genetic structures most likely contributes to the rapid spread of carbapenem- and aminoglycoside-resistant genes among the Acinetobacter clinical population.