Mechanisms of antibiotic resistance development in bacterial pathogens

点击翻译按钮获取中文摘要

Project Summary: Microorganisms evolve quickly under selective conditions and can rapidly adapt to environmental changes. We recently discovered that transcription-coupled repair (TCR), and, encounters between the DNA replication and transcription machineries (conflicts) increase mutagenesis significantly in specific genes. We subsequently identified the factors required for these mutagenesis mechanisms. We now find that these factors promote antibiotic resistance development in bacteria. Here, using various experimental techniques, we plan to investigate the impact of TCR and conflicts on evolution of antibiotic resistance in important human pathogens, as well as deepen our understanding of the underlying mechanisms promoting this adaptive process. We are putting forth a research program with a novel approach to circumvent a global health crisis: a study tailored towards characterization of potential drug targets that promote evolution of antibiotic resistance in bacterial pathogens.