Developing novel antibiotics
Andrew M. Gulick, Ph.D.

gulickMuch has been written lately about the potential that we are entering a post-antibiotic era. Many of the common drugs that have been used to treat infections are becoming less effective as bacteria develop natural strategies to elude the toxic effects of the current arsenal of drugs. This is forcing scientists to identify new essential pathways that bacteria need to establish or maintain an infection. These pathways may contain targets that can be exploited for novel antimicrobial compounds

The Gulick lab is studying important biochemical pathways from the human pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae that cause infections of pneumonia and also infections of the eye, liver, or skin. These pathways make complicated chemicals that the bacteria needs during the establishment of an infection. For example, bacteria need iron as an essential nutrient to grow. Humans maintain large pools of iron that are tightly sequestered, making it unavailable for bacteria to use. To establish an infection, bacteria need to "steal" this iron.

Pseudomonas and Klebsiella use interesting chemical strategies to make unique molecules that effectively steal the iron from human cells and serum. Bound to these carrier molecules, the iron is then transported back into the bacterial cell. The Gulick lab is studying many proteins in these biochemical pathways to understand why they are essential for bacteria and to identify ways to block their action. They have identified “pre-therapeutic” chemicals that block specific steps in these processes. The goal is to test the ability of these compounds to prevent bacterial cell growth in a variety of disease-like environments.

A long-term goal is the development of new antibiotic compounds that could inhibit the bacterial infections caused by these bacteria. During the last five years, this project has been supported by grants from the National Institutes of Health, the Cystic Fibrosis Foundation, and the Max and Victoria Dreyfus Foundation.

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