2024/10/25 by My Tran, Angel J Hernandez Viera, Patricia Q. Tran +3 · 2 voices
Biochemistry, Genetics and Molecular Biology · Environmental Science · Immunology and Microbiology · #Bacteriophages and microbial interactions #Genomics and Phylogenetic Studies #Microbial infections and disease research
paper · pdf · doi:10.7554/elife.102743
openalex publication_date 2024/10/25 · openalex created_date 2024/10/26 · openalex updated_date 2026/07/29
Bacteriophage (phage) therapy is a promising means to combat drug-resistant bacterial pathogens. Infection by phage can select for mutations in bacterial populations that confer resistance against phage infection. However, resistance against phage can yield evolutionary trade-offs of biomedical relevance. Here, we report the discovery that infection by certain staphylococcal phages sensitizes different strains of methicillin-resistant Staphylococcus aureus (MRSA) to β-lactams, a class of antibiotics against which MRSA is typically resistant. MRSA cells that survive infection by these phages display significant reductions in minimal inhibitory concentration against different β-lactams compared to uninfected bacteria. Transcriptomic profiling reveals that these evolved MRSA strains possess highly modulated transcriptional profiles, where numerous genes involved in S. aureus virulence are downregulated. Phage-treated MRSA exhibited attenuated virulence phenotypes in the form of reduced hemolysis and clumping. Despite sharing similar phenotypes, whole-sequencing analysis revealed that the different MRSA strains evolved unique genetic profiles during infection. These results suggest complex evolutionary trajectories in MRSA during phage predation and open up new possibilities to reduce drug resistance and virulence in MRSA infections.