Plasmid-mediated antimicrobial resistance in Gram-negative bacteria

The epidemiology of resistance plasmids is a major issue for the description of antimicrobial resistance diffusion. The identification of related plasmids associated to specific resistance genes may help to follow the spread of epidemic plasmids, opening new epidemiological scenarios on the mechanism of diffusion of antimicrobial resistance. This aspect is particularly interesting when applied to collections of plasmids that are playing a major role in the diffusions of Extended Spectrum Beta Lactamases (ESBLs) such as CTX-M, SHV, TEM. The aim of this thesis is the molecular characterization of plasmids conferring drug resistances in different collections of Enterobacteriaceae of human and animal origin. Several example of epidemic plasmids will be discussed: the IncHI2 plasmids carrying blaCTX-M-9 or blaCTX-M-2 genes identified from human and animal isolates of Escherichia coli and Salmonella from Spain, Belgium and UK; the IncI1 family of plasmids characterized by specific virulence factors, carrying the blaCMY-2, blaTEM-52 and blaCTX-M-1 genes from Salmonella and E. coli of human and animal origin; the IncN plasmids carrying the gene codifying the metallo-β-lacatamase VIM-1 from human isolates of Klebsiella pneumoniae and E. coli in Greece; the IncA/C2 plasmids carrying specific resistance genes such as blaCMY-2, blaCMY-4, blaVIM-4 and blaVEB-1 from different Enterobacteriaceae isolated worldwide; different plasmid replicons (IncFII, IncA/C1, IncI1) carrying the ESBL SHV-12 from human and animal origin. The comparative analysis of plasmid backbones allowed to ascertain the diffusion of common, emerging plasmids and helped to determine the evolution of these plasmids by acquisition of relevant resistance genes by a panoply of mobile genetic elements and illegitimate recombination events.