Researchers discover how phage resistance contributes to the emergence of dominant strains of Salmonella

Researchers from the Quadram Institute and the University of East Anglia have discovered how resistance has contributed to the emergence of dominant strains of Salmonella. In addition to antimicrobial resistance, bacteriophage resistance can give these insects a boost, at least in the short term.

With the rise in antimicrobial resistance, the search for new ways to combat disease-causing bacteria is ongoing.

One line of research concerns a natural enemy of bacteria – viruses. There are more virus particles on Earth than there are stars in the universe, and some of them specialize in using bacteria to replicate. These viruses, called bacteriophages, also kill their bacterial hosts, making them potential new allies in the fight against bacterial infections.

One of the main causes of bacterial diseases in the world is Salmonella bacteria. They cause 78 million cases of disease each year and many of these are attributed to a closely related group of Salmonella that infect humans and animals; Salmonella enterica serovar Typhimurium, or S. Typhimurium for short.
Salmonella The success of Typhimurium is due to its genetic flexibility which allows it to adapt and overcome resistance. This has led to waves of related strains that dominate for 10-15 years but are then replaced by new strains. These new strains may show better resistance to efforts to control them, making the design of new interventions like trying to hit a moving target.

Professor Rob Kingsley of the Quadram Institute and the University of East Anglia and his team have supported efforts to combat Salmonella by studying its genome for clues about its adaptability, and how changes in the genetic code have given the strains a competitive edge. A 2021 study, for example, revealed how Salmonella carves out a place in pork production.

In a new study, recently published in the journal Microbial genomicsthey have now focused on the influence of bacteriophage resistance on circulating populations of Salmonella, and how this predator-prey relationship has co-evolved. The research was funded by the Biotechnology and Biological Sciences Research Council, part of UK Research and Innovation.

It’s a complex relationship – while bacteriophages attack bacteria, they can also stimulate the spread of genetic material between strains. Indeed, the spread of genetic variation and the transfer of resistance genes among bacterial populations can be mediated by phages – a process known as phage-mediated transduction.

“There is renewed interest in using phages as an alternative or accompaniment to antibiotic treatment of bacterial infections, and like antibiotics, the clue to understanding the potential emergence of resistance to phage therapy lies in how whose resistance emerges in nature.said Professor Rob Kingsley.
In collaboration with the UK Health Safety Agency (UKHSA) and the Animal and Plant Health Agency (APHA), scientists examined whole genome sequences of strains collected from human and animal infections over the last decades.

They found that strains of Salmonella those best adapted to life in livestock, and therefore most likely to cause disease in humans, tend to be more resistant to bacteriophages. Phage resistance may help bacteria invade new environmental niches

The current dominant strain, ST34, in addition to being multi-drug resistant, also exhibits greater resistance to bacteriophage attack than its ancestors. This appears to be due to the acquisition of phage genetic material in its genome – a step that increased its resistance to bacteriophage attack.
But this leads to an intriguing situation, because phage resistance means that these bacteria are less likely to acquire new genetic material, including resistance genes through phage-mediated transduction. So, could the short-term gain of phage resistance have long-term consequences leaving the bacterium unable to adapt to changes in its environment such as societal interventions or even new antimicrobial treatments? Surveillance data suggests this opens the door for another clone to emerge to replace it.
Whatever the situation, it is clear that genomic monitoring of these bacteria and their bacteriophages is necessary to ensure that we recognize and can respond to any new emerging threats. And the more we learn about how these microbes co-evolve, the more likely we are to counter their threats to human health.