Factors that cause trimethoprim resistance in Streptococcus pyogenes

Area of Science:

• Microbiology
• Antimicrobial Resistance
• Molecular Biology

Background:

• Trimethoprim use for Streptococcus pyogenes infections has been limited due to perceived widespread resistance.
• Understanding the prevalence and genetic basis of trimethoprim resistance in S. pyogenes is crucial for clinical decision-making.

Purpose of the Study:

• To investigate the extent and molecular mechanisms of trimethoprim resistance in Streptococcus pyogenes isolates.
• To identify specific genetic factors contributing to trimethoprim resistance in S. pyogenes.

Main Methods:

• Susceptibility testing of S. pyogenes isolates from India and Germany against trimethoprim and trimethoprim-sulfamethoxazole (SXT).
• Screening for known horizontally transferable dihydrofolate reductase (dfr) genes (dfrG, dfrF, dfrA, dfrD, dfrK) in resistant isolates.
• Nucleotide sequencing of the intrinsic dfr gene in isolates lacking transferable resistance genes.

Main Results:

• Approximately 25.7% of S. pyogenes isolates from India exhibited trimethoprim resistance.
• The dfrF gene was the most prevalent resistance factor in India (60.9%) and the sole factor in resistant German isolates (4/5).
• An amino acid substitution in intrinsic dihydrofolate reductase conferred resistance in some S. pyogenes isolates lacking other dfr genes.

Conclusions:

• Trimethoprim resistance in S. pyogenes is significant, with the dfrF gene being a primary driver.
• The findings suggest trimethoprim might be viable for S. pyogenes treatment, but the spread of resistance mechanisms warrants monitoring.