09/27/18 - 9:45 AM to 10:45 AM
Sigma-Aldrich Seminar: Professor John S. Blanchard
Probing Bacterial Antibiotic Resistance: Failing to Achieve Irrelevance
Antibacterials were discovered in the 1930’s, -40’s and 50’s and represent one of the most important eras of drug discovery to reduce human mortality in its history. Most, but not all, were identified from bacterial or fungal cultures, and used for obtaining a selective growth and survival advantage. Within years of the introduction of each successive class of antibacterials into clinical use, resistance to that antibiotic class was observed. For over thirty years, the Blanchard lab has studied the mechanisms of resistance to various classes of antibacterials, and focused on those that are enzymatically mediated. We have defined structures and mechanisms of several of enzymes that generate aminoglycoside resistance and β-lactam resistance. We also discovered a novel mechanism for generating fluoroquinolone resistance. While we hoped the pharmaceutical industry would try to develop inhibitors to the expression or activity of these systems, or be immune to their action – “resisting resistance” – in fact the opposite has occurred, with almost no pharmaceutical company investing in this research, but rather dropping antibacterial discovery efforts completely. As a result the rise in life-threatening infections due to drug-resistant bacteria is on the rise, as is the cost of treatment, and mortality. Three different systems will be explored in this presentation.
Professor Blanchard's research
John Blanchard is professor of biochemistry and the Dan Danciger Professor of Biochemistry at Albert Eistein College of Medicine. His research group is engaged in the structural and functional characterization of enzymes from Mycobacterium tuberculosis. Researchers have discovered new drug combinations that are effective against strains of this drug-resistant Tuberculosis. They also are determining the mechanisms of resistance to broad-spectrum antibiotics, in particular, the aminoglycoside class of antibacterials, and are developing new methods to identify the large number of proteins that are known to be post-translationally modified by lipidation, including both myristoylation and palmitoylation.