Turns Out Natural Antibiotics Also Help Bacterial Communities Grow

One of the most fruitful sources of antibiotics are bacteria them​selves. Some two-thirds of all naturally occurring antibiotics come via the single bacterial genus Streptomyces, ranging from the very early-days streptomycin, a compound usually credited with being the first effective tuberculosis treatment, to more recent antibiotics-of-last-resort known as carbapenems. Bacterially-derived antibiotics can be astoundingly effective, but come with the same risks as any other microbial: rapidly-accelerating resistance.

Understanding why bacteria make these antibiotics may offer crucial insights into how we use them in the first place. Because, clearly, we are mis​using them.

One likely answer is described ​in the current Proceedings of the National Academy of Sciences, which comes courtesy of biologists at the University of North Carolina. In short: Bacteria don't intend to create bacteria "killing machines" at all. That just happens to be a rather human-friendly (if often too friendly) side effect of a broader plan. What bacteria are really after, at least in some large part, are biofilms, which are vast communities of bacteria that spread as thin sheets across a surface.

That bacteria form biofilms in response to their own antibiotics—antibiotics that have historically been considered "secondary" products—isn't a new observation, but it's usually been regarded as a side effect rather than a primary purpose.

"Biofilms are communities of bacterial cells living in a sticky, self-produced extracellular matrix on either a liquid or solid surface," the current study explains. "The formation of bacterial biofilms can be both beneficial—such as on plant roots or in wastewater treatment plants—or detrimental—such as on in-dwelling [catheters, breathing tubes, etc.] medical devices or during infection. Thus, understanding the chemical signals that induce and inhibit biofilm formation in bacteria has broad relevance."

As a biofilm or biofilm-in-process, the bacteria become something of a pseudo-organism, with individual members capable of cellular differentiation—becoming biofilm producers, for example. Bacillus subtilis, the bacterial species studied here, is often used in research as a model organi​sm for this reason. In particular, Bacillus subtilis, a bacteria often found in grass or hay, produces a class of compounds known as thiazolyl peptides.

"Thiazolyl peptides are known antibiotics produced by diverse bacterial taxa," the PNAS paper notes. "It has been believed that antibiotics are deployed by bacteria as weapons, providing them with an evolutionary advantage over other microbes. We show here that these weapons can also act as chemical tools that elicit biofilm production in the model bacterium Bacillus subtilis. Importantly, the biofilm-inducing (and therefore signaling) properties of these compounds are independent of their killing activity."

Given that we use these antibiotics exclusively for their killing ability, this could be a crucial revelation. If we're effectively arming bacteria for biofilm production by the very compounds intended for bacterial annihilation, we have a problem.

"That suggests that antibiotics can independently and simultaneously induce potentially dangerous biofilm formation in other bacteria and that these activities may be acting through specific signaling pathways," notes Elizabeth Shank, the study's lead author, in a statem​ent. "It has generated further discussion about the evolution of antibiotic activity, and the fact that some antibiotics being used therapeutically may induce biofilm formation in a strong and specific way, which has broad implications for human health."

We still have a lot to learn about thiazolyl peptides, particularly how the signalling mechanism works to shape and grow interspecies bacterial communities. "Future experiments using reconstituted synthetic systems or natural environments seeded with specific microbes should allow us to evaluate the effects of the [wild-type or antibiotic-null versions of the thiocillins," Shank and co. write.

The answer is hardly in ditching natural antibiotics altogether. As Shank notes, they've proven to be "exquisite tools" in the fight against infections. This is one potentially huge step toward using them better.