Study holds phages responsible for superbug emergence

Scientists from the University of Pittsburgh School of Medicine unraveled that phages—small viruses that attack bacteria—are responsible for the initiation of rapid bacterial evolution that leads to the rise of treatment-resistant “superbugs.” The study results have been published in the journal Science Advances.

Study holds phages responsible for superbug emergence
Vaughn Cooper, Ph.D., Professor of microbiology and molecular genetics, University of Pittsburgh School of Medicine. Image Credit: Vaughn Cooper.

The scientists demonstrated that unlike the popular theory in the field of evolutionary microbiology, the means of diversification and adaptation in bacterial colonies did not originate from a homogenous clonal population.

Surprisingly, they identified that most of the early adaptations were not random point mutations, but phages, normally considered as bacterial parasites, gave the bacteria the evolutionary advantages to the winning strains very early.

Essentially, a parasite became a weapon. Phages endowed the victors with the means of winning. What killed off more sensitive bugs gave the advantage to others.”

Vaughn Cooper, PhD, Study Senior Author and Professor, Microbiology and Molecular Genetics, University of Pittsburgh

With bacteria, an attentive observer can easily track evolution within a couple of days. Since bacteria tend to grow rapidly, it easily acquires new traits or develops resistance to antimicrobial drugs with a few days.

The scientists match the bacterial infections to a film played from the middle. It is more like late-arriving moviegoers struggling to mentally reconstruct events that led to a scene unfolding in front of their eyes. Medical practitioners are compelled to make decisions on treatment footed on a static snapshot of when a patient presents at a hospital.

Furthermore, similar to the movie theatre, the physicians cannot verify if their predictions about the infection were wrong or right.

The current study reveals that phage and bacterial evolutions often go side by side, particularly during the early phases of bacterial infection. It is a multi-layered process, wherein bacteria and phages combine in a chaotic dance, continuously interacting and co-evolving.

While tracking alterations in genetic sequences of six bacterial strains in a skin wound infection in pigs, the researchers discovered that the jumping of phages from one bacterial host to another was uncontrolled. Even those clones that did not gain an evolutionary advantage presented with phages integrated into their genomes.

A majority of the clones had more than one phage incorporated in their genetic material—mostly, there were two, three, or even four phages in one bug.

It showed us just how much phages interact with one another and with new hosts. Characterizing diversity in early bacterial infections can allow us to reconstruct history and retrace complex paths of evolution to a clinical advantage. And, with growing interest in using phages to treat highly resistant infections, we are learning how to harness their potency for good.”

Vaughn Cooper, PhD, Study Senior Author and Professor, Microbiology and Molecular Genetics, University of Pittsburgh

Source:
Journal reference:

Marshall, C. W., et al. (2021) Rampant prophage movement among transient competitors drives rapid adaptation during infection. Science Advances. doi.org/10.1126/sciadv.abh1489.

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