When we think about bacteriophages, we don’t typically think of cooperation. Commonly represented with six legs and a big “head”, bacteriophages can look more like a bug than a microbial predator. Bacteriophages, a type of virus, attack by injecting their DNA into their bacterium target, making the DNA a part of the bacterium’s own genetic code. More and more bacteriophages grow inside the bacteria and, eventually, break through the bacteria’s cell membrane to find their next victims. Usually, this results in the death of the host bacterium, but some bacteriophages are slightly more gentle. Instead of killing their host, some filamentous bacteriophages slow the bacterium’s growth and make their membranes more porous. This method of viral replication still typically kills the bacterium, but there are exceptions.
Paul Turner, Yale professor of Ecology and Evolutionary Biology, and Jason Shapiro, a former Yale PhD candidate who currently works at Loyola University Chicago, were investigating microbial relationships between the M13 filamentous bacteriophage and E. coli , a common bacterium. What started out as a parasitic relationship developed into a mutually beneficial partnership between the two microbes, an unusual result. The researchers knew they had uncovered an important discovery regarding the evolutionary relationship between E. coli and the M13 bacteriophages and set out to further investigate and analyze this relationship.
The researchers took six evolved M13 populations from the previous experiment, where the relationship was initially discovered, to use for this new study. ninety-six-well microplates of E. coli were mixed with the phage populations. In almost every case, a mutualistic relationship was once again developed after about 130 bacterial generations, but the findings still perplexed Shapiro. “We still don’t really understand the mechanism behind this benefit,” he said. However, they do have several hypotheses. “This phage was already known to change the bacterial membrane during infection, and a side effect of this is the bacteria becoming more porous,” Shapiro said. This is usually harmful for the bacteria because it increases their sensitivity to the surrounding environment. However, because this study took place in a solution that did not have any harmful chemicals, it could have made survival easier. More pores in the membrane of the bacteria could mean increased access to resources.
To further investigate the mechanism mystery, some of the bacteriophages and E. coli were sequenced. The researchers compared the DNA of the evolved and unevolved microbes in an effort to discover where the populations diverged. Mutations were discovered mostly in genes that the bacteriophage uses for replication. “[These genes] haven’t been implicated in previous work for affecting bacterial growth, and it’s not known how changes to phage replication would help the [infected] bacteria grow faster than uninfected bacteria,” Shapiro said.
It’s a little easier to answer who was evolving. According to Shapiro, the bacteriophage and bacteria evolved together to develop mutualistic relationships, but each case was slightly different. “In some cases, the newly evolved phages only help their new coevolving bacteria,” Shapiro said. “In others, the phage benefits both their coevolving bacteria and the unevolved bacteria.” In the former scenario, he hypothesized that the bacteria evolved to tolerate the bacteriophage infection, which meant they were able to experience the mysterious increased growth rate due to the bacteriophage. But in the latter, it seems that only the bacteriophage evolved. This evolution still somehow resulted in a mutualistic relationship, even though the bacteriophage was already benefitting from the bacteria.
This study could be helpful to our understanding of disease and bacteria evolution. “Understanding how the phage and bacteria coevolve when the phage appears to be helping the bacteria, including understanding any tradeoffs associated with this evolution, would be useful for understanding how phages that do affect diseases have evolved with their hosts,” Shapiro explained. With so many potential paths to explore, it remains to be seen just how far-reaching the implications of this research can be for treatment of diseases.