Study of sRNA-regulated Transposition of IS Element Carrying Antibiotic Resistant Genes

Multiple drugs resistance (MDR) pathogens have become a serious threat to human health. The antibiotics resistant genes in the conjugative plasmids that commonly found in clinical isolates are often associated with the mobile genetic elements such as insertion sequence (IS). Although this phenomenon has been known for over 40 years, the regulation of IS and their function in mobilizing and clustering the antibiotics resistant genes in plasmids or bacteria remains unclear. Small RNA regulation is one of focusing areas in bacterial gene expression in response to external stimuli and it has been shown recently to control the transposition of certain insertion sequences. Previously, we isolated and sequenced several MDR plasmids carrying extended-spectrum β-lactamase genes from clinical isolate. Moreover, sRNA and transcriptomic sequencing analysis of these plasmids identified the antisense sRNAs that overlap with the genes of transposases, which possibly regulate the transposition of IS26 and ISEcp1. IS26 and ISEcp1 are the commonly found IS elements carrying antibiotics resistant genes in MDR plasmids. In this project, we set out to characterize the cis-encoded sRNA, as-tnp26, and its interaction with IS26 transposase mRNA in controlling IS26 transposition efficiency. Moreover, the underlying mechanism of disseminating antibiotics resistant genes via IS26 transposition in bacteria will be elucidated. In addition, we will determine the stresses conditions that can activate IS26 transposition through the regulation of as-tnp26 sRNA and further studied their mechanisms. Understanding the roles of IS elements in mobilization and clustering preference of antibiotics resistant genes will provide insights to the prevalence of MDR plasmids among bacteria, and their dissemination in the community. Moreover, the knowledge of sRNA-regulated transposition will guide us to a better control of the emerging MDR pathogens from preventing the spreading of antibiotics resistant genes.