Staphylococcal Phages Adapt to New Hosts by Extensive Attachment Site Variability

Area of Science:

• Microbiology
• Virology
• Genetics

Background:

• Prophages in bacterial pathogens often encode virulence factors.
• Sa3int phages in human Staphylococcus aureus promote immune evasion.
• Sa3int phages are now found in livestock-associated MRSA (LA-MRSA).

Purpose of the Study:

• Investigate Sa3int phage integration in LA-MRSA strains with mutated primary integration sites.
• Understand the adaptation mechanisms of Sa3int phages in alternative integration sites.
• Determine the role of phage recombinase in Sa3int phage establishment in LA-MRSA.

Main Methods:

• Deep sequencing to analyze phage integration events.
• Nucleotide sequence analysis of phage attachment sites.
• Investigating the activity of phage-encoded tyrosine recombinase.

Main Results:

• Sa3int phages adapt via nucleotide changes in attachment sequences to increase homology with alternative bacterial sites.
• This adaptation significantly enhances phage integration in subsequent infection rounds.
• Promiscuity of the tyrosine recombinase facilitates Sa3int phage establishment in LA-MRSA.

Conclusions:

• Phages can adapt and establish in bacterial strains lacking ideal integration sites through population heterogeneity.
• This phage adaptation increases the virulence and zoonotic potential of LA-MRSA.
• Findings have broader implications for other phages and phage-mediated bacterial evolution.