PITTSBURGH, July 16, 2021 – For the first time, researchers at the University of Pittsburgh School of Medicine discovered that phages – tiny viruses that attack bacteria – are key to initiating rapid bacterial evolution that leads to the emergence of treatment-resistant “superbugs”. The results were published in today Scientific advances.
The researchers showed that, contrary to a prevailing theory in evolutionary microbiology, the adaptation and diversification process in bacterial colonies does not start from a homogeneous clonal population. They were shocked to discover that much of the early adaptation was not due to random point mutations. Instead, they found that phage, which we normally refer to as bacterial parasites, gave the winning strains the evolutionary advantage early on.
“Essentially, a parasite became a weapon,” said Vaughn Cooper, Ph.D., a professor of microbiology and molecular genetics at Pitt. “Phages provided the winners with the means to win. What killed more sensitive bugs gave others an advantage. “
When it comes to bacteria, an attentive observer can follow their evolution within a few days. Due to the rapid growth of bacteria, it only takes days for strains of bacteria to acquire new properties or develop resistance to antimicrobial drugs.
The researchers compare the way bacterial infections occur in the clinic to a film that is played from the middle. Just as late-arriving moviegoers have difficulty mentally reconstructing events that led to a scene in front of their eyes, doctors are forced to make treatment decisions based on a static snapshot of a patient’s imagination in the hospital. And just like in a movie theater, there is no way to rewind the film and verify that the guesswork 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. This is a complex process in which phages and bacteria are connected in a chaotic dance, constantly interacting and evolving together.
When the scientists tracked changes in the genetic sequences of six bacterial strains in a skin wound infection in pigs, they found that phage jumping from one bacterial host to another was widespread – even clones that did not gain evolutionary advantage had phages in theirs Genomes. Most clones had more than one phage integrated into their genetic material – often there were two, three or even four phages in one beetle.
“It showed us how much phages interact with each other and with new hosts,” said Cooper. “Characterizing diversity in early bacterial infections can allow us to reconstruct history and trace complex evolutionary pathways back to clinical benefit. And with the growing interest in using phages to treat highly resistant infections, we are learning how we can use their potency sustainably. “
Other authors on the study are Christopher Marshall, Ph.D., and Christina Lim, Ph.D., of Marquette University; and Erin Gloag, Ph.D., and Daniel Wozniak, Ph.D., of Ohio State University.
This work was supported by the National Institutes of Health Grants R01AI134895, R01AI143916, U01AI124302, and R33HL137077, and the American Heart Association Career Development Award (19CDA34630005).
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About the University of Pittsburgh School of Medicine
As one of the nation’s premier academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science in a wide range of disciplines to harness the power of new knowledge and improve the human condition. Mostly driven by the School of Medicine and its affiliates, Pitt has been a top 10 recipient of a grant from the National Institutes of Health since 1998. In the rankings recently published by the National Science Foundation, Pitt was ranked fifth among all American universities overall scientific and technical research and development support.
Likewise, the School of Medicine is committed to improving the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, empathetic clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has worked with the university to raise the standard of medical excellence in Pittsburgh and position healthcare as the driving force behind the region’s economy. Further information on the medical faculty can be found at http: // www.
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