Researchers shocked to discover bacterial parasites behind the rise of “superbugs”

For the first time, researchers at the University of Pittsburgh School of Medicine have discovered that phages – tiny viruses that attack bacteria – are essential for initiating rapid bacterial evolution leading to the emergence of resistant “superbugs” to treatments. The results were published today in Scientists progress.

The researchers showed that, contrary to a dominant theory in the field of evolutionary microbiology, the process of adaptation and diversification of bacterial colonies does not start from a homogeneous clonal population. They were shocked to find that the cause of much of the early adaptation was not random point mutations. Instead, they found that phages, which we normally think of as bacterial parasites, are what gave winning strains the evolutionary advantage early on.

“Essentially, a parasite has become a weapon,” said senior author Vaughn Cooper, Ph.D., professor of microbiology and molecular genetics at Pitt. “The phages gave the victors the means to win. What killed the most sensitive insects gave the advantage to others.

When it comes to bacteria, a keen observer can follow the development in a matter of days. Due to the speed with which bacteria grow, it only takes a few days for bacterial strains to acquire new characteristics or develop resistance to antimicrobial drugs.

Researchers compare the way bacterial infections present in the clinic to a film shown in the middle. Just as late-arriving moviegoers find it difficult to mentally reconstruct the events that led to a scene unfolding before their eyes, doctors are forced to make treatment decisions based on a static snapshot of when a patient presents to the hospital. And just like in a movie theater, there’s no way to rewind the movie and check if their guess about the plot or the origin of the infection was right or wrong.

The new study shows that bacterial and phage evolution often go hand in hand, especially in the early stages of bacterial infection. It is a multi-layered process in which phages and bacteria are joined in a chaotic dance, constantly interacting and co-evolving.

When scientists tracked changes in the genetic sequences of six bacterial strains in a skin wound infection in pigs, they found that phage skipping from one bacterial host to another was endemic – even those clones that didn’t. have not obtained an evolutionary advantage had phages incorporated into their genomes. Most clones had more than one phage built into their genetic material – there were often two, three, or even four phages in an insect.

“It showed us how well phages interact with each other and with new hosts,” Cooper said. “Characterizing the diversity in early bacterial infections can allow us to reconstruct the history and trace complex evolutionary pathways with clinical benefit. And, with increasing interest in using phages to treat highly resistant infections, we are learning to harness their power for good. “

Reference: July 16, 2021, Scientists progress.

Other authors of the study include Christopher Marshall, Ph.D., and Christina Lim, Ph.D., of Marquette University; and Erin Gloag, Ph.D., and Daniel Wozniak, Ph.D., from Ohio State University.

This work was supported by National Institutes of Health Grants R01AI134895, R01AI143916, U01AI124302, and R33HL137077, and the American Heart Association Career Development Award (19CDA34630005).