Researchers have provided the first direct evidence of a mildly pathogenic microorganism evolving to defend its host from a more pathogenic invader. Their research indicates a potential pathway for evolution towards host-microbe mutualism.
Host-microbe interactions, such as those that occur in the human gut, are critical to sustaining host health. These beneficial relationships may come in the form of microbial vitamin production, toxin degradation, or even pathogen protection.
Direct evidence for the origins of these specialized host-microbe mutualisms, however, is lacking.
Scientists often refer to mutualistic relationships as having an “adaptive origin”. In other words, some selective pressure must have driven the evolution of a given host-microbe mutualism.
To directly test one of the proposed adaptive origins of host-microbe mutualism, a research group led by Dr. Kayla King at the University of Oxford studied host-microbe interactions in one of geneticists’ favorite model organisms: the Caenorhabditis elegans worm, or, C. elegans.
Specifically, the scientists were testing the hypothesis that a mildly pathogenic bacterium found naturally in the gut system of C. elegans can evolve to defend its host from a more pathogenic (higher mortality-inducing) invading bacterium.
Evidence for this evolution of protective behavior may indicate the first step on a path toward host-microbe mutualism.
To test their hypothesis, the research team allowed the mild pathogen, Enterococcus faecalis, to colonize the gut of C. elegans. Once established, the worms were exposed to a highly pathogenic bacterium, Staphylococcus aureus.
The experiment was run for 15 C. elegans generations. For each successive generation, E. faecalis cells in worm guts were extracted and used to colonize the subsequent C. elegans generation before addition of S. aureus. This created a consistent and long-term interaction between the two bacterial species within the host.
Six separate experiments, each with the same multi-generational evolution design were conducted as replicates.
At the end of the experiments, the genome and biochemical activity of the resulting E. faecalis population was examined to determine whether forced interaction with a dangerous pathogen inside the host had any effect on the evolution of the mild, naturally occurring pathogen.
Indeed, the researchers found that all six independent experiments had caused E. faecalis to increase its production of an antimicrobial compound called superoxide.
The production of this antibiotic is a key way in which bacteria compete and attack one another in the natural environment, indicating that exposure to a foreign, highly pathogenic invader caused the resident mild pathogen to ramp up its defenses.
Most importantly, in doing so, the host was protected from infection.
Interestingly, the multi-generational evolution experiment did not cause any attenuation of E. faecalis pathogenesis. In other words, although the mild pathogen evolved a mechanism for defending its host from a more serious infection, the mild pathogen retained its own ability to cause host mortality.
The results of this study support the hypothesis that one adaptive origin of host-microbe symbiosis could be the route from pathogen to mutualist.
In nature, when coupled with a reduction in pathogenicity, a previously pathogenic microorganism’s ability to kill more dangerous invaders could be selected for within a host and persist, eventually leading to the development of more specialized host-microbe interactions.