Researchers discover how phage resistance helps drive the emergence of dominant strains of Salmonella

Researchers from the Quadram Institute and the University of East Anglia have discovered how resistance has helped drive 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 of antimicrobial resistance, research is underway for new ways to fight disease-causing bacteria.

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

One of the leading causes of bacterial disease globally are Salmonella bacteria. They are responsible for 78 million cases of the 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, o St. Tifimurio in brief.
Salmonella Typhimurium’s success is due to its genetic flexibility which allows it to adapt and overcome resistance. This has resulted in 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, which makes for 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 fight Salmonella studying its genome for clues about its adaptability and how changes in the genetic code have given varieties a competitive edge. A 2021 study, for example, found how Salmonella carves out a niche in pork production.

In a new study, recently published in the journal Microbial genomicshave now examined the influence of bacteriophage resistance on circulating populations of Salmonella, and how this predator-prey relationship 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: as bacteriophages prey on bacteria, they can also increase the spread of genetic material between strains. This is because the spread of genetic variation and the transfer of resistance genes between bacterial populations can be mediated by phages, a process known as phage-mediated transduction.

There is growing interest in using phages as an alternative to or as an accompaniment to antibiotic treatment for bacterial infections, and like antibiotics, the clue to understanding the potential emergence of resistance to phage therapy is in how resistance emerges in naturesaid the prof. Rob Kingsley.
Working with the UK Health Security Agency (UKHSA) and the Animal & Plant Health Agency (APHA), the scientists examined the whole genome sequences of strains collected from human and animal infections over the past few decades.

They found that the strains of Salmonella better adapted to living in livestock, and thus those more likely to cause disease in humans, tend to be more resistant to bacteriophages. Phage resistance would appear to help bacteria invade new environmental niches

The current dominant strain, ST34, in addition to being resistant to multiple drugs, also shows 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, as 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 in phage resistance lead to long-term consequences leaving bacteria unable to adapt to changes in their environment such as societal interventions, even new antimicrobial treatments? Surveillance data suggests this opens the door for another clone to emerge to replace it.
Whatever the situation, what is clear is that genomic surveillance 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 coevolve, the better chance we have of countering their threats to human health.

Source:

Magazine reference:

Charity, OJ, et al. (2022) Increase in phage resistance through lysogenic conversion accompanying the emergence of the monophasic Salmonella Typhimurium ST34 pandemic strain. Microbial genomics. doi.org/10.1099/mgen.0.000897.

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