Researchers are investigating how phage resistance helps control the emergence of dominant Salmonella strains

Researchers are investigating how phage resistance helps control the emergence of dominant Salmonella strains

Researchers from the Quadram Institute and the University of East Anglia have revealed how resistance helped drive the emergence of dominant strains Salmonella. In addition to antimicrobial resistance, resistance to bacteriophages may give these bugs a boost, at least in the short term.

With the rise of antimicrobial resistance, new ways to fight disease-causing bacteria are being sought.

One line of research deals with the 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 them. These viruses, called bacteriophages, also kill their bacterial hosts, making them potential new allies in the fight against bacterial infections.

They are one of the main causes of bacterial diseases worldwide Salmonella bacteria. It accounts for 78 million cases of the disease each year, many of which are attributed to the closely related group Salmonella which infect humans and animals; Salmonella enterica serovar Typhimurium, or WITH. typhimurium for short.
Salmonella Typhimurium’s success lies in its genetic flexibility, which allows it to adapt and overcome resistance. This has led to waves of related strains that dominate for 10 to 15 years, but are then replaced by new strains. These new strains may show greater resistance to efforts to control them, making designing 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 are supporting the fight effort Salmonella by studying its genome to find clues to its adaptability and how changes in the genetic code gave the strains a competitive advantage. For example, a 2021 study revealed how Salmonella creates a gap in pork production.

In a new study, recently published in the journal Microbial Genomicsnow investigated the effect of bacteriophage resistance on circulating populations salmonella, and how this predator-prey relationship co-evolved. The research was funded by the Biotechnology and Life Sciences Research Council, part of UK Research and Innovation.

It’s a complex relationship—while bacteriophages hunt bacteria, they can also promote 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 renewed interest in the use of phages as an alternative or adjunct to antibiotic treatment of bacterial infections, and as with antibiotics, the key to understanding the potential emergence of resistance to phage therapy lies in how resistance occurs in nature.” said Professor Rob Kingsley.
Working with the UK Health Safety Agency (UKHSA) and the Animal and Plant Health Agency (APHA), the researchers examined the whole-genome sequences of strains collected from human and animal infections over the past few decades.

They found that tribes Salmonella best adapted to life in farm animals, and thus those most likely to cause disease in humans tend to be more resistant to bacteriophages. Phage resistance appears to help bacteria invade new niches in the environment

The current dominant ST34 strain, in addition to being multidrug resistant, also exhibits greater resistance to bacteriophage challenge than its progenitors. This appears to be due to it acquiring phage genetic material into its genome – a step that has increased its resistance to bacteriophage attack.
However, this leads to an interesting 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 lead to long-term consequences that make bacteria unable to adapt to changes in their environment, such as societal interventions, even new antimicrobial treatments? Surveillance data suggests that this opens the door for another clone to emerge to replace it.
Whatever the situation, it is clear that genomic surveillance of these bacteria and their bacteriophages is necessary to ensure that we recognize and can respond to any emerging threats. And the more we learn about how these microbes co-evolve, the better chance we have of countering their threats to human health.


Link to journal:

Charity, OJ, et al. (2022) Enhanced phage resistance through lysogenic conversion accompanying the emergence of a monophasic pandemic strain of Salmonella Typhimurium ST34. Microbial Genomics.

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