One of the most serious problems in global public health today is the increasing incidence of antibiotic resistant bacterial infections. Of particular concern is the emergence of Enterobacteriaceae that are resistant to carbapenems, the class of antibiotic considered the last resort for treating increasingly resistant organisms. While uncommon prior to 1992, their prevalence has risen at an alarming rate and infection with these resistant pathogens is associated with increased mortality.
Resistance to carbapenems is primarily due to acquisition of carbapenem-hydrolyzing ß-lactamases or carbapenemases. Among the enterobacteria harboring carbapenemase-encoding genes, Klebsiella pneumoniae is the most common, having rapidly become endemic in many hospital settings around the world. Outbreaks of carbapenemase-producing K. pneumoniae have been reported in at least 36 states in the United States though predominantly in the northeast, as well as Brazil, Israel, Greece, India, and sporadic detection of isolates in other parts of the world.
While a large variety of these enzymes belong to three classes of ß-lactamases, the rapid global spread of carbapenem-resistant Enterobacteriaceae has largely been attributed to transmission of clonal strains (e.g., ST 258), with horizontal gene transfer of the KPC ß-lactamase being the most common. These genes are associated with a Tn3-based transposon, Tn4401, suggesting that this transposon contributes to the mobilization and dissemination of the KPC genes.
In this project we examine and track the genetic relationship of a collection of carbapenem-resistant enterobacterial isolates from several healthcare facilities in Boston and California using a whole genome sequencing approach. In parallel we have also collected a number of carbapenem-susceptible strains for comparative purposes. Results from our analysis will contribute to the understanding of the specific genetic mechanisms underlying phenotypic differences in drug susceptibility in enterobacterial species, while providing the nucleotide-based resolution of strain differences required to describe the epidemiology of the spread of antibiotic resistance in a clinical setting.
Project Data can also be found at NCBI
Please cite all data relating to this initiative (including individual genes and genomes) as:
"Carbapenem Resistance initiative, Broad Institute (broadinstitute.org)"