Class 1 integrons and their impact on the mobility of antibiotic resistance in clinical environments

Antibiotic resistance in pathogenic bacteria is becoming an increasingly important issue in the management of infectious diseases. Mortalities resulting from the inability to treat infections caused by resistant organisms have been recorded in significant numbers around the world. Mobile genetic elements such as integrons, transposons and gene cassettes, along with the lateral gene transfer which occurs between them, are largely responsible for the spread of resistance genes amongst pathogenic Gram negative bacteria. Integrons are gene expression systems capable of capturing and disseminating mobile gene elements such as gene cassettes. These gene cassettes, when associated with clinical integrons, predominantly code for antibiotic resistance genes. The fact that integrons allow both the integration and excision of multiple gene cassettes leads to the efficient spread of multi-drug resistance amongst pathogenic bacteria. This project investigates antibiotic resistance in Escherichia coli by examining class 1 integrons within several contexts. A collection of 718 E. coli isolates were obtained from clinical sources, primarily originating from urinary tract infections. These isolates were typed for antibiotic resistance capabilities and tested for class 1 and 2 integron presence. Integron cassette arrays were characterized, sequenced and mapped. In the collection, 23% of isolates carried class 1 integrons, while 3% carried a class 2 integron. Eight distinct cassette arrays were detected, consisting of gene cassettes solely from the aadA and dfrA families. Since identical integrons and cassette arrays appeared in a range of E. coli phylotypes and clonal lines, there appears to be significant and ongoing lateral gene transfer between E. coli lineages.