Changes in the agr locus affect enteritis caused by methicillin-resistant Staphylococcus aureus.

Area of Science:

• Microbiology
• Infectious Diseases
• Genetics

Background:

• Methicillin-resistant Staphylococcus aureus (MRSA) can cause enteritis, a gastrointestinal infection.
• The accessory gene regulator (agr) is a global virulence regulator in Staphylococcus aureus, controlling the expression of various toxins and exoproteins.
• Previous studies suggested a link between MRSA enteritis and phenotypic/genotypic changes, hypothesizing agr as a key factor.

Purpose of the Study:

• To investigate the role of the accessory gene regulator (agr) locus in the development of MRSA-associated enteritis.
• To compare the expression levels of agr components and toxin genes in MRSA strains causing enteritis versus those not associated with enteritis.
• To identify specific mutations within the agr locus associated with MRSA enteritis.

Main Methods:

• Analysis of 12 MRSA isolates from enteritis stool samples and 17 MRSA isolates not associated with enteritis.
• Genotyping of MRSA strains using pulsed-field gel electrophoresis (PFGE).
• Quantitative reverse transcription-PCR (qRT-PCR) to measure RNAII, agrA, RNAIII, and tst gene expression.
• Sequencing of the agr locus to identify mutations.

Main Results:

• MRSA isolates associated with enteritis exhibited higher expression of agrA, RNAIII, and tst compared to non-enteritis isolates.
• Nearly all clinical isolates showed similar RNAII expression levels.
• All MRSA enteritis isolates possessed agr mutations, with many sharing specific mutations, particularly in the agrA C-terminal region, unlike most non-enteritis isolates.

Conclusions:

• Mutations in the agr locus are strongly associated with MRSA enteritis.
• These agr mutations appear to modify the expression of agrA and RNAIII, potentially leading to increased toxin production.
• The observed changes in virulence factor expression due to agr mutations likely contribute to the pathogenesis of MRSA enteritis.