From Ants to Antibiotics:
The Curious Course of Cameron Currie
Can insects help physicians treat antibiotic-resistant bacterial infections? University of Wisconsin-Madison researcher Dr. Cameron Currie and his collaborators believe they just might. With the support of American Recovery and Reinvestment Act (ARRA) funding awarded by the National Institutes of Health (NIH) Common Fund, Currie and his colleagues are investigating whether select species of ants and other insects may be rich sources of new antibiotics. If so, their research may lead to the development of new medications needed to stay ahead of rapidly developing drug resistance in disease-causing bacteria. Growing resistance to the current armamentarium of antibiotics is a potentially devastating threat to human health and one of the greatest challenges confronting medicine today.
If the idea of screening insects for novel antibiotics sounds new, that’s because it is. While the majority of antibiotics in clinical use are derived from natural sources, they traditionally have been isolated from soil which contains a diverse array of microorganisms. Even so, surveying soil samples is laborious and expensive, and only rarely yields a previously unknown antibiotic or one suitable for human use. Consequently, there is an urgent need for new antibiotic sources that can be screened more easily and economically, and are more likely to yield unique antimicrobial agents.
Insects, like humans and other organisms, must contend with bacteria, and have evolved mechanisms to combat these pathogens. While still a graduate student, Currie discovered that the leaf-cutter ants he was studying use antibiotics to eradicate specialized parasites that infect the fungus gardens the ants cultivate as a food source (yes, leaf-cutter ants are farmers). “These are beneficial bacteria that actually grow on the body of the ants and produce antibiotics” explains Currie, “The ants can sense infection [in the fungal garden] and rub their body against areas of infection to apply the antibiotic.”
The group of bacteria the leaf-cutter ants associate with is called actinobacteria which is well-known for producing pharmaceutically important small molecules including antibiotics. Indeed, the majority of antibiotics used to combat infection in humans are derived from actinobacteria.
From Ants to Antibiotics
His realization that the leaf-cutter ants associate with the same group of bacteria that is the source of most human antibiotic therapies, led to what Currie describes as more of a “Ha ha” than an “Aha” moment: “I was actually joking around at first. It was like, well, [leaf-cutter ants] farmed for tens of millions of years before [humans] did, wouldn’t it be funny if they utilized bacterial production of antibiotics for millions of years before we did? And, it was one of those things ‘Hey, maybe they did!’”
It’s Not Just Ants
Subsequent research by Currie and others has revealed that some species of wasps and beetles also associate with bacteria for the production of antibiotics. “We have studied these bacteria from many different insects now and the historical work started with the ant system but the vast majority of the strains that we’re working on now for the ARRA are from other insect systems.” Collectively, these findings suggest that insect-associated bacteria might be a promising source for drug discovery.
The Insect Advantage
Currie and his colleagues believe that surveying bacteria-associating insects offers a more direct and less labor-intensive route to discovering novel small molecules than soil sampling. And, as Currie explains, their data bears this out, “We’re finding new antibiotics, 1 per 5-to-10 strains that we look at, so our rate of discovery [in bacteria-associating insects] is significantly higher than in soil.” This higher discovery rate, Currie speculates, may reflect two factors: (1) he and his collaborators are analyzing a previously untapped source of antibiotics; and (2) they are surveying a system in which a host organism may be selecting bacteria to associate with specifically for its ability to produce antibiotics. As a result, the searches conducted by Currie and his colleagues are more targeted and less hit-and-miss than surveys of free-living bacteria in the soil.
Pursuing Drug Leads
Potentially novel small molecules isolated by Currie and his colleagues will be screened for antibacterial, antifungal, and antiviral activities at the University of Wisconsin-Madison small molecule sequencing facility. Using this technology, Currie believes, will greatly accelerate the pace of the research: “One of our other goals and hopes is to capitalize on new sequencing technology in terms of driving our small molecule discovery. It’s an exciting time from that perspective. I don’t think people have really completely capitalized yet on that from a natural product discovery perspective.” Small molecules that pass this test will be examined for toxicity, stability, and efficacy in a mouse model system, an increasingly critical step in moving drug discovery forward. Currie hopes to take several small molecules through testing in this system.
Benefits of the ARRA Funding
ARRA funding of the Currie project is fulfilling immediate economic and longer term scientific goals set forth by the Recovery Act. In terms of economic benefits, ARRA funding has allowed Dr. Currie and his collaborators to hire one post-doctoral fellow, three research technicians, and several undergraduate student lab assistants. With respect to longer-term biomedical benefits, ARRA funding is allowing Dr. Currie and colleagues to explore how a topic of more general scientific interest—understanding symbiotic associations between antibiotic-producing bacteria and diverse host organisms—may be applied to drug discovery and reducing the rapidly expanding health threat posed by bacterial drug resistance.