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Trimethoprim resistant dihydrofolate reductases in normal faecal flora isolated in India
1Department of Medical Microbiology, University of Edinburgh Medical School, Scotland.
Abstract:
A high incidence of resistance to trimethoprim has been shown in the normal faecal flora in a population in south India. The dihydrofolate reductase (dhfr) genes mediating transferable resistance to trimethoprim have been identified. Unusually, in this study, the dhfrV was shown to be the predominant resistance gene (dhfrV 50% of transconjugants, dhfrIa 30%), the dhfrIb was also detected being distinguished from the dhfrV by an oligo-probe. However, when non-transferable resistance was considered, the dhfrIa was the most prevalent of the dhfrs identified. All those plasmids harbouring the dhfrIa were shown to possess Tn7. All the plasmids that probed positive for the dhfrV and the dhfrIb were shown to be associated with the integrase of the Tn21-like transposons, but 8 of the dhfrV genes were not associated with the Tn21 resolvase. The dhfrIV was shown to be present in all seven plasmids that produced low level trimethoprim-resistance. The dhfrV, first characterized in Sri Lanka, would seem to have a local distribution in this region of Asia but is distinguishable from the dhfrIb only by the use of an oligo-probe.
Insights
Trimethoprim resistance is high in South Indian gut bacteria, with dihydrofolate reductase (dhfr) V genes being most common in transferable resistance. Non-transferable resistance primarily involves dhfr Ia genes.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- High incidence of trimethoprim resistance observed in fecal flora of a South Indian population.
- Trimethoprim resistance is often mediated by dihydrofolate reductase (dhfr) genes.
Purpose of the Study:
- Identify and characterize dhfr genes responsible for transferable and non-transferable trimethoprim resistance in the studied population.
- Investigate the genetic elements associated with these resistance genes.
Main Methods:
- Analysis of transconjugants to identify transferable trimethoprim resistance genes.
- Oligonucleotide probe hybridization to distinguish between different dhfr gene variants (dhfrV, dhfrIa, dhfrIb).
- Plasmid analysis to identify associated mobile genetic elements like Tn7 and Tn21-like transposons.
Main Results:
- The dhfrV gene was the predominant transferable resistance gene (50%), followed by dhfrIa (30%).
- The dhfrIa gene was most prevalent in non-transferable resistance.
- Plasmids carrying dhfrIa were associated with Tn7, while dhfrV and dhfrIb were linked to Tn21-like transposons, though some dhfrV lacked Tn21 resolvase.
- dhfrIV was found in plasmids conferring low-level trimethoprim resistance.
Conclusions:
- The dhfrV gene, previously identified in Sri Lanka, appears to have a local distribution in Asia.
- Distinct genetic elements are associated with different dhfr gene variants and their transferability.
- Understanding the prevalence and genetic context of these resistance genes is crucial for antimicrobial stewardship.