Researchers discover how phage resistance helps emerge 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, resistance to bacteriophages can give these insects a boost, at least in the short term.

With the emergence of antimicrobial resistance, new ways to combat pathogenic bacteria are being sought.

One line of research looks at a natural enemy of bacteria: viruses. There are more virus particles on Earth than there are stars in the universe, and some of these 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.

Being one of the leading causes of bacterial disease worldwide Salmonella bacteria. They are responsible for 78 million cases of illness each year, many of which are attributed to a closely related group Salmonella that infect humans and animals; Salmonella enterica serovar Typhimurium, or S. Typhimurium in brief.

Salmonella Typhimurium’s success is due to its genetic flexibility that allows it to adapt and overcome resistance. This has led to waves of related species that dominate for 10 to 15 years, but are then replaced by new species. These new species can be more resistant to attempts to control them, making designing new interventions akin to trying to hit a moving target.

Professor Rob Kingsley of the Quadram Institute and the University of East Anglia and his team are supporting the fight against the virus Salmonella by studying its genome to find clues to its adaptability and how changes in the genetic code have given species a competitive advantage. For example, a 2021 study revealed how Salmonella conquers a niche in pork production.

In a new study, recently published in the journal Microbial genomicsthey have now looked at the influence of bacteriophage resistance on the 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.

This is a complex relationship – although bacteriophages prey on bacteria, they can also stimulate the spread of genetic material across strains. That’s because the spread of genetic variation and transfer of resistance genes between bacterial populations can be mediated by phages – a process known as phage-mediated transduction.

There is a renewed interest in the use of phages as an alternative or an accompaniment to antibiotic treatment for bacterial infections, and as with antibiotics, the clue to understanding the potential emergence of resistance to phage therapy is the way resistance in the nature arises.said Prof. Rob Kingsley.
Working with the UK Health Security Agency (UKHSA) and the Animal & Plant Health Agency (APHA), the scientists examined whole genome sequences of strains collected from human and animal infections over the past few decades.

They found that the tensions of Salmonella best adapted to life in livestock, and so those most likely to cause disease in humans are usually more resistant to bacteriophages. Phage resistance appears to help bacteria penetrate new environmental niches

The current dominant strain, ST34, is not only resistant to multiple drugs, but also shows higher resistance to attack by bacteriophages than its ancestors. This appears to be because the phage incorporated genetic material into its genome – a step that increased its resistance to bacteriophage attack.
But this leads to an intriguing situation, because resistance to phages 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 from phage resistance lead to long-term consequences, preventing the bacteria from adapting to changes in its environment, such as societal interventions, even new antimicrobial treatments? Surveillance data suggests this opens the door to the emergence of another clone to replace it.
Whatever the situation, it is clear that genomic surveillance of these bacteria and their bacteriophages is needed to ensure that we recognize and respond to new emerging threats. And the more we learn about how these microbes evolve together, the more likely we are to counter their threats to human health.

Source:

Magazine reference:

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

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