Many of the antibiotics we rely on are produced by bacteria immune to their product. Conventional thinking on the evolutionary benefit of these potent drugs has been challenged with a new study suggesting they have more complex and interesting applications than previously realized. It is hoped that a better understanding of the uses bacteria find for antibiotics could help us develop new and better targeted versions.
While the original antibiotic came from a fungus, bacteria are not united in some sort of alliance against the rest of the tree of life. Streptomycin, for example, comes from the Gram-positive Streptomyces griseus bacterium and is effective against many deadly Gram-negative species, including those responsible for tuberculosis and plague.
"For a long time we've thought that bacteria make antibiotics for the same reasons that we love them—because they kill other bacteria," says Dr. Elizabeth Shank of the University of North Carolina at Chapel Hill. "However, we've also known that antibiotics can sometimes have pesky side-effects, like stimulating biofilm formation." Biofilms are groups of microorganisms whose cells stick together on a surface and are bound together by a slimy collection of extracellular DNA, proteins and carbohydrates.
But Shank now proposes in the Proceedings of the National Academy of Sciences that sometimes biofilm production is anything but a side effect. In previous research, she found that the bacterium Bacillus cereus releases a signaling compound that causes another bacterium, Bacillus subtilis, to form biofilms. While both bacterial species are found in soil, B. subtilis also inhabits the human gastrointestinal tract. Now, Shank has identified the signaling mechanism as thiocillin, a type of antibiotic produced by many bacterial species.
The authors established that the thiocillin-producing gene is found in other bacteria not previously known as antibiotic producers. Modification of the struture of the thiocillin produced revealed that it would still cause B. subtilis to form biofilms. “Importantly, the biofilm-inducing (and therefore signaling) properties of these compounds are independent of their killing activity,” the paper notes.
Shank points out that biofilms help bacteria “survive an attack.” However, she adds, “It was always thought this was a general stress response. Our finding indicate this isn't true. We've discovered an antibiotic that very specifically activates biofilm formation and does so in a way that has nothing to do with its ability to kill.” The biofilm triggering effect could even predate its use as a mechanism for killing rivals, Shank believes.
The work opens up a number of promising lines of research. For one, Shank says, “some antibiotics being used therapeutically may induce biofilm formation in a strong and specific way, which has broad implications for human health." On the other hand, a better understanding of which bacterial species produce antibiotics and why could help replenish our depleted stocks of medicines that are still effective. Finally, the research raises the question of how the two Bacillus species interact, and what B. cereus gains from getting B. subtilis to form biofilms.