research groups
Mechanisms of Bacterial Resistance to Antibiotics
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- Morán Barrio, Jorgelina
- Marchiaro, Patricia
- Giacone, Lucía
- Morales Flores, Ailen Micaela
- Cavatorta, Matias
RESEARCH LINES
Antimicrobial multiresistance in Acinetobacter baumannii analyzed from a multifactorial perspective. Evolution and dissemination of plasmids carrying OXA-type carbapenemase genes in clinical strains of local origin. Biogenesis of these enzymes
Antimicrobial resistance in A. baumannii has a multifactorial basis and includes the production of oxacillinases (OXA) endowed with carbapenemase activity, mainly acquired from horizontal gene transfer (HGT). Our objective is elucidating the molecular basis of evolution and dissemination of blaOXA genes among multiresistant clones of A. baumannii. The blaOXA gene is the main responsible of carbapenem resistance among local strains and is bounded with recognition sites for the XerC/D site-specific recombinases. Our hypothesis is that these sites participate in the mobilization of blaOXA genes to other genomic locations or plasmids by recombination events. We study the role of plasmidic XerC/D sites in the evolution of resistance plasmids and HGT mechanisms involved in their dissemination among the clinical A. baumannii population. The carbapenemase OXA-58 is exported to the bacterial periplasm as a lipoprotein in the form of cargo of outer membrane vesicles, thus contributing to bacterial multiresistance. The biogenesis mechanism of these vesicles and their role in multiresistance are also subjects of our study. Principal investigators: J. Morán Barrio – A. Limansky – A. Viale.
Pseudomonas (P. putida group) and Acinetobacter bereziniae as environmental reservoirs of blaVIM-2 y blaNDM-1 metallo-beta-lactamase genes conferring carbapenem resistance. Genetic platforms responsable of the dissemination and clinical impact
The emergence of nosocomial strains resistant carbapenem antibiotics is mainly due to intragenomic events involving the mobilization of carbapenemase genes including metallo-beta-lactamase (MBL) genes, added to horizontal gene transfer (HGT). It is therefore relevant to elucidate the contribution of each of these events to the evolution of this resistance. In this context, and under the hypothesis that resistance genes emerge in bacteria subjected to antimicrobial selective pressure, it is essential to characterize genetic platforms carrying MBL genes of both ample dissemination (blaVIM-2), as well as recently occurring (blaNDM-1). We study with this objective the molecular basis of dissemination of these MBL genes in microbial organisms that constitute environmental reservoirs, with special emphasis in the genus Pseudomonas and Acinetobacter, including Pseudomonas putida group species and A. bereziniae. An increase knowledge of the evolution and dissemination of these genes from these reservoirs to pathogenic and multiresistant opportunistic species will certainly contribute to the control of nosocomial infections. Principal investigators: A. Limansky – A. Viale – J. Morán Barrio.
Role of proteins secreted in association to outer membrane vesicles to the physiopathology of Acinetobacter barumannii
baumannii pathogenesis is associated to antimicrobial multiresistance (MR) and to virulence factors still poorly characterized. There is a growing evidence that the outer membrane vesicles (OMV) are vehicles to transport bacterial proteins that contribute to the establishment of the infection. Our goal is to study the contribution of secretion proteins with special emphasis in lipoproteins, to the pathogen survival under stress conditions that mimic the contact with the host. We focus in particular in proteins secreted in association with A. baumannii OMV, with the aim to increase significantly our understanding of their role in the physiopathology of this organism. This, in turn, will reveal new targets for the development of therapeutic drugs. Principal investigator: J. Morán Barrio.
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