University of Wisconsin Team Shreds Expectations in Search for New Antibiotics
Dr. David Andes discusses how he and researchers at UW-Madison are finding antibiotics from sources such as ants, and the potential of translating the discovery into new therapies for patients.
Madison, Wisconsin - Two years into a five-year study seeking new sources of antibiotics, a University of Wisconsin-Madison research team has found more than 400 compounds potentially useful in combating antibiotic-resistant infections.
The team’s initial goal was to find 20 such compounds per year.
“In the first two years we have found more than 400 compounds,” said Dr. David Andes, professor of medicine and division chief of infectious diseases at the UW School of Medicine and Public Health. “Now, we are working to find the best of those 400. We are finding new compounds at a greater rate than expected. Overall, the study is exceeding expectations.”
Andes is a co-principal investigator on a $16 million National Institutes of Health (NIH) grant awarded to UW-Madison in 2014. The other is Cameron Currie from the department of bacteriology in the UW College of Agricultural and Life Sciences. Other members of the team are Tim Bugni, Michael Hoffman, Dr. Bruce Klein, Dr. Rod Welch and Harvard researcher Jon Clardy.
The study is unique in both how and where the team is looking. Traditionally, soil has been mined for antibiotics. But, Andes said, the study of soil has become a dead end because the same drugs are turning up over and over again.
Hence, the UW-Madison team has been studying other sources of natural products from insects and marine environments.
In addition, the team of scientists has found unique methods to find these new antibiotics including rapid identification based upon searching the genome and metabolism of the antibiotic-producing microbes.
“Our team has developed a completely new paradigm for anti-infective drug discovery. It’s a group of scientists all thinking about the same problem,” said Andes. The past two years the team has been all over the United States, including Alaska and Hawaii.
The team is targeting two major groups of infections: fungi associated with infections in immunocompromised patients like cancer and transplant patients, and drug resistant bacteria responsible for the majority of U.S. hospital infections.
The Wisconsin antimicrobial drug discovery research center includes more than 50 staff working on this particular research in the field, harvesting insects and marine life and in the lab sequencing the genomes of each microbe to determine if it merits further testing and if the microbe has ever been found before. They also attempt to coax an organism to make compounds by mimicking its environment in the laboratory. The last new antibiotic discovered was in 1987. Andes said there has been more than an 80 percent decrease in development of antibiotics since that time.
“There are no new classes of antibiotics and the rediscovery rate is 99.5 percent so the common sentiment is that the well is dry,” said Andes. The U.S. Centers for Disease Control and Prevention says more than two million drug-resistant infections a year are reported.
“There are patients in almost every hospital with infections that have absolutely no treatment options,” said Andes. In the 1980s, pharmaceutical companies were seeking Food and Drug Administration (FDA) approval of 10 to 20 antibiotics a year. “We want to get back to the ’heyday’ of antibiotic discovery.”
The UW Antimicrobial Drug Discovery and Development Center was established in 2007. The Wisconsin Partnership Program and various NIH Challenge grants funded the research.
Date Published: 04/25/2016