Factors That Cause Trimethoprim Resistance in Streptococcus pyogenes

Abstract

ABSTRACTThe use of trimethoprim in treatment ofStreptococcus pyogenesinfections has long been discouraged because it has been widely believed that this pathogen is resistant to this antibiotic. To gain more insight into the extent and molecular basis of trimethoprim resistance inS. pyogenes, we tested isolates from India and Germany and sought the factors that conferred the resistance. Resistant isolates were identified in tests for trimethoprim or trimethoprim-sulfamethoxazole (SXT) susceptibility. Resistant isolates were screened for the known horizontally transferable trimethoprim-insensitive dihydrofolate reductase (dfr) genesdfrG,dfrF,dfrA,dfrD, anddfrK. The nucleotide sequence of the intrinsicdfrgene was determined for resistant isolates lacking the horizontally transferable genes. Based on tentative criteria, 69 out of 268 isolates (25.7%) from India were resistant to trimethoprim. Occurring in 42 of the 69 resistant isolates (60.9%),dfrFappeared more frequently thandfrG(23 isolates; 33.3%) in India. ThedfrFgene was also present in a collection of SXT-resistant isolates from Germany, in which it was the only detected trimethoprim resistance factor. ThedfrFgene caused resistance in 4 out of 5 trimethoprim-resistant isolates from the German collection. An amino acid substitution in the intrinsic dihydrofolate reductase known from trimethoprim-resistantStreptococcus pneumoniaeconferred resistance toS. pyogenesisolates ofemmtype 102.2, which lacked other aforementioneddfrgenes. Trimethoprim may be more useful in treatment ofS. pyogenesinfections than previously thought. However, the factors described herein may lead to the rapid development and spread of resistance ofS. pyogenesto this antibiotic agent.