Elucidating transmission of plasmids harboring blaKPC among carbapenem-resistant Enterobacteriaceae using long-range sequencing

PROJECT NARRATIVE: Carbapenem-resistant Enterobacteriaceae (CRE) pose an escalating antibiotic-resistant threat to public health and appear to be diversifying. The proposed research will examine transmission of carbapenem resistance genes between different species of Enterobacteriaceae via mobile plasmids using state-of-the-art long-range sequencing technology in order to 1) systematically assess the incidence of plasmid transmission in a CRE- endemic hospital and identify “hypertransmissible” plasmids contributing to CRE diversification; 2) assess specific clinical factors contributing to CRE colonization or infection following horizontal transfer; and 3) use phylogenetic analyses to determine whether hospital environmental surfaces are reservoirs for plasmids encoding carbapenem resistance genes, potentiating their persistence and spread. If successful, this study will clearly demonstrate the important contribution of plasmids to the dissemination of CRE, identify targets for enhanced surveillance, and validate the integration of long-range plasmid into effective CRE surveillance approaches accounting for the plasmid-mediated spread of CRE.