Two leading scientists in the MSU Department of Microbiology and Molecular Genetics, Victor DiRita
, Rudolph Hugh Endowed Chair in microbial pathogenesis, and Neal Hammer
, assistant professor, are also using these labs to fuel their research.
"We are moving toward precision-based targeting where we discover how the bacteria function in order to disarm them, not necessarily to kill them," says Victor DiRita, Rudolph Hugh Endowed Chair in microbial pathogenesis whose lab studies the Gram-negative bacteria devastating hospitals known as Carbapenem-Resistant Enterobacteriaceae. "This approach is smart and targeted — this is a laser beam, not a sledgehammer."
"With some microbes, we have identified small, potentially therapeutic molecules that stop the production of an important toxin by understanding the important microbial pathways that turn on toxins and cause the host problems," DiRita explains. "This next generation of antibiotics won't kill bacteria — they will protect it from being lethal."
The Hammer lab aims to limit the infectious capacity of the Gram-positive pathogen methicillin-resistant Staphylococcus aureus, or MRSA, by screening MSU's growing library of new plant-based compounds for ones that will inhibit its metabolic pathways.
"Through our research, we know that S. aureus has an interesting pathway of becoming resistant to several classes of antibiotics — it switches its metabolism to a small colony variant, or SCV," Hammer says. "This is somewhat good news because our work, and work done by many other labs, demonstrated that S. aureus only uses two metabolic pathways to proliferate during infection, aerobic respiration and fermentation. SCVs rely on fermentation."
Metabolically speaking, S. aureus is somewhat similar to humans. When we exercise, oxygen becomes limiting and lactic acid is produced via fermentation — hence sore muscles. S. aureus, in SCV form, also makes lactic acid as a fermentative end-product.
"We can force S. aureus into a fermentative, SCV state with a class of drug treatment called aminoglycocides," Hammer says. "My research program is interested in finding compounds in our chemical library that selectively kill these SCVs to design a combinatorial therapy that potentiates the activity of the aminoglycocides."
"Fundamentally, we are biologists who are curious about bacteria and how they work and, if they are harming people, how we can stop them from working," DiRita adds. "If this is a space race, we are John Glenn circling the earth."
Vaccines providing alternatives
MSU Biomedical Engineering and Chemistry
Professor Xuefei Huang
strives to provide a complementary approach to antibiotic discovery through his work on vaccines.
Huang is examining the role carbohydrates play in inflammation, tumor metastasis and both bacterial and viral infections. He strives to create vaccines for a variety of diseases, including bacterial infections.
"Our interest is finding a way to target carbohydrates to generate immune responses that will protect against bacterial infection," Huang says. "The vaccine approach is complementary to antibiotics, in the sense that the reason we are using a vaccine is to prevent the infection, and antibiotics are used to kill the infection."