Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistant Staphylococcus...

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 is a significant pathogen.
• A variant acquiring mosaic Φ11 prophage (mΦ11) causes skin and soft tissue infections, with increased abscess size.
• The mechanism by which mΦ11 enhances virulence is not fully understood.

Purpose of the Study:

• To elucidate the mechanism by which mΦ11 enhances CA-MRSA virulence in skin infections.
• To identify specific genes and pathways regulated by mΦ11 that contribute to virulence.
• To understand the role of epigenetic regulation in bacterial adaptation and spread.

Main Methods:

• Genetic inactivation of mΦ11-encoded genes, including the adenine methyltransferase (pamA).
• Assessment of abscess size and skin inflammation in vivo.
• Quantitative reverse transcription-PCR to measure gene expression (fnbA).
• Biofilm formation assays.

Main Results:

• The mΦ11-encoded adenine methyltransferase (pamA) is responsible for increased abscess size and skin inflammation.
• pamA upregulates the expression of fibronectin-binding protein A (fnbA).
• Inactivation of fnbA abrogates pamA-mediated virulence, identifying fnbA as a pamA-specific virulence factor.
• pamA promotes in vivo biofilm formation in skin abscesses, linked to FnBPA.

Conclusions:

• Phage-mediated epigenetic regulation of staphylococcal gene expression is a critical mechanism for virulence.
• pamA, an mΦ11-encoded DNA methylase, enhances S. aureus virulence by upregulating fnbA expression.
• This mechanism drives adaptive evolution in S. aureus, facilitating the spread of virulent clones.