Applying Basic Bacteriology to the Global Health Challenges of Infectious Disease
2008-10 Seed Grant
Zemer Gitai's team is helping tackle the challenge of antibiotic resistance through the development of new classes of antibiotic drugs. The need for such new drugs is particularly acute because nearly all antibiotics currently in use target the same small set of bacterial processes, resulting in the rise of multi-drug resistance. Fortunately, the past decade of basic research from several groups, including Gitai, has identified several new classes of molecular mechanisms that are essential for bacterial survival and pathogenesis.
To date, such basic studies of bacterial cell biology have focused on non-pathogenic species. By re-directing his lab’s expertise to focus on the important human pathogen, Pseudomonas aeruginosa, Gitai discovered that this bacterium uses polar localization of its virulence factors to mediate pathogenesis. To infect, P. aeruginosa uses flagella, propeller-like tails, and type IV pili, shorter structures that function somewhat like grappling hooks. After initial infection, P. aeruginosa forms biofilms for better growth and increased antibiotic resistance. If the flagella or pili are mislocalized, meaning they are not placed at one of the poles of the bacteria, the bacterium has reduced infection strength.
Through a separate chemical screening approach, Gitai's team also recently identified a small molecule that targets the essential bacterial cytoskeleton. Preliminary studies suggest that this simple and inexpensive compound can block the growth and virulence of a wide range of human pathogens. These findings form the seeds for their new investigations into how bacterial cell biology can be used to combat bacterial pathogenesis.
Natsai Nyakudarika ’08, William Dixon ’09, and Jonathan Turner ’10 have pursued advanced research inquiry on P. aeruginosa flagellar localization through a sequence of investigative work, including a mentored summer internship, junior independent work, and ultimately the senior thesis.
Gitai was awarded the National Institute of Health Director’s New Innovator Award for project Discovering Antibiotic Drugs & Targets Via High-Throughput Bacterial Cell Biology, that emerged from his Health Grand Challenge award.
The next steps are to continue characterizing the novel antibiotic compound they discovered as well as both the mechanisms and significance of the polar localization of P. aeruginosa virulence factors.
- Molecular Biology