Sean Pidgeon of the Pires Research Group

Graduate Student Sean Pidgeon will present

Bacterial Cell Surfaces: Exploiting the Antibiotic Resistant Pathway

on October 2, 2018 at 4:10 PM in Neville Hall, Room 3

The worldwide problem of antibiotic resistance has become one of the most serious health threats of the 21st century and will undoubtedly become a top clinical priority. In the U.S. alone, antibiotic-resistant bacteria cause at least 2 million infections and 23,000 deaths a year resulting in a $55-70 billion per year economic impact. The rise in the number of resistant bacteria is mainly attributed to the improper and overuse of antibiotics, and the ability of these bacteria to evolve elaborate systems to counteract pharmaceuticals. As the number of efficacious antibiotics continues to rapidly dwindle without replenishment, the possibility of entering a postantibiotic era can become a reality. To combat this ever-growing threat, the Centers of Disease Control and Prevention (CDC) stress four core actions; (1) preventing infections from occurring and spreading, (2) tracking resistant bacteria, (3) improving the use of antibiotics, and (4) promoting the development of new antibiotics and new diagnostic tests for resistant bacteria.  With those actions in mind, our goal is to rededicate efforts towards understanding fundamental bacterial physiology and pathology, with a special focus on mechanisms related to drug resistance. A clearer understanding of the molecular events underpinning antibiotic resistance phenotypes can be instrumental in guiding the design of next generation antibiotics.  Some of the most potent antibiotics in use today are molecules that inhibit the assembly of the bacterial cell wall. More specifically, they block peptidoglycan (PG) biosynthesis, a major constituent of the cell wall. The unique structure of PG relative to human cellular components makes it an ideal target for drug development. Despite the tremendous clinical importance of bacterial cell wall targeted antibiotics, it is surprising that several key aspects of PG biosynthesis and processing remain poorly characterized. While it has long been known that PG alterations in response to antibiotics are operative in the acquisition of drug resistance, there are few cellular reporter molecules available to track and quantify PG structural changes in live bacterial cells. We set out to build synthetic cell wall analogs that track PG alterations. These reporter molecules will unveil mechanistic insights into the molecular modifications that endow bacteria with drug resistance to -lactams and glycopeptides.