New Antibiotics and Enzyme Inhibitors against Gram-Positive and Gram-Negative Bacteria

This thesis is organized in five chapters describing the efforts towards investigating new antibacterial agents for the treatment of Gram-positive and Gram-negative bacterial infections. The introduction of antibiotics into medical science was deemed as one of the most important successes of the twentieth century. However, the improper and overuse of antibiotics result in antibiotic resistance, which is now recognized as a worldwide threat to the public health. The bacteria that are studied in this thesis are Enterococcus faecium, Pseudomonas aeruginosa and Acinetobacter baumannii.

E. faecium is a Gram-positive bacterium; P. aeruginosa and A. baumannii are Gram-negative bacteria. The Centers for Disease Control and Prevention reports that each year thousands of people die because of the E. faecium, P. aeruginosa and A. baumannii resistant infections. In this thesis, I describe the discovery of new antibiotics that originated from computational screening and their lead optimization. I also describe efforts in study of compounds that would circumvent the resistance problem.