As more antibiotic-resistant “superbugs” emerge, it’s clear that we desperately need new antimicrobial drugs. Yet, over the past couple of decades, antibiotic discovery has largely been stagnant.
“The reality is there’s almost no new antibiotics that are developed. And that’s because pharmaceutical companies have decreased their investment—in part because of the rediscovery issue,” explains bacteriology professor Cameron Currie.
The “rediscovery issue” refers to the fact that soil has historically been the prime source of new antibiotics—but it seems to be tapped out. When scientists screen soil microbes for new antibiotics, they keep finding the same compounds over and over again.
Currie is part of a team that is looking elsewhere.
Currie and his colleagues have been focusing their efforts on microbes that are associated with insects, plants and marine life from all around the United States, funded by a $16 million grant from the National Institutes of Health that was awarded in 2014.
“One of the major hurdles is finding new compounds, and that’s where we’re really excelling,” says Currie, a co-principal investigator on the grant. His partner is David Andes in the UW–Madison School of Medicine and Public Health.
At the front end, the work involves some good old-fashioned bioprospecting. Currie’s group, which is in charge of the terrestrial sphere, has gathered more than 2,000 flies, aphids, caterpillars, bees, ants and other insects, as well as mushrooms and plants, from locales near and far, including Alaska, Hawaii and Wisconsin’s Devil’s Lake.
Back at the lab, things get high-tech pretty quickly. Microbes are isolated from the samples and tested for antimicrobial activity. Promising strains undergo genetic sequencing that allows Currie’s group to determine how likely they are to produce novel antibiotic compounds. From there, other scientists involved in the grant go on to test the most promising compounds in a mouse model of infection. This approach has already yielded some exciting drug candidates.
“We have 9,000 strains to screen, and we have already found some new compounds that are effective at combating infections in mice and have low toxicity,” says Currie.
With so many samples to process, Currie’s group adopted bar code technology to help them keep track. They have a bar code reader—like you’d find in a grocery store— connected to a lab computer that they use to scan petri dishes, look up samples and add new data. For each microbial strain they’ve isolated, the database has photos of the “host” insect or plant, GPS coordinates for the collection site, assay results, genetic sequence and much more.
At this point, Currie feels confident that the project will pay off, and he’s eager to see one of the group’s compounds go into human clinical trials.
“If you find one new antibiotic that gets used in treatment, it’s a major success. You’re saving people’s lives,” Currie says.