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The following is a summary of “Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant Staphylococcus aureus,” published in the December 2024 issue of Infectious Disease by Li et al. 

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of severe endovascular infections, with the prophage-encoded protein Gp05 playing a key role in MRSA persistence during vancomycin (VAN) treatment, though the mechanisms behind this persistence remain unclear.  

Researchers conducted a retrospective study to examine the genetic factors contributing to Gp05-associated MRSA persistence.  

They utilized RNA sequencing (RNA-seq) on an isogenic MRSA strain set, which included a clinically persistent bacteremia isolate (PB 300-169), its isogenic chromosomal gp05 deletion mutant, and gp05-complemented strains.  

The results showed that RNA-seq analysis revealed significant downregulation of the graSR-vraFG regulatory system and its downstream genes, mprF, and dltABCD, in the gp05 deletion mutant compared to the wild-type and gp05-complemented strains. This downregulation caused a notable shift in cell membrane composition, with an increase in negatively charged phosphatidylglycerol (PG) and a decrease in positively charged lysyl-PG (LPG), and the lipid changes led to heightened susceptibility of the gp05 deletion mutant to human cationic antimicrobial peptide (CAMP) LL-37, polymorphonuclear neutrophils (PMN), and VAN. Similar results were found in an isogenic gp05 overexpression strain set with a different genetic background (MRSA USA300 JE2).  

Investigators concluded that Gp05 played a crucial role in MRSA persistence by influencing cell surface properties, suggesting potential therapeutic targets for combating persistent MRSA infections. 

Source: academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiae640/7935184