What is it about?
Variations in the gene in Pneumocystis jirovecii for DHFR, the target of the drug trimethoprim, suggested the possibility that clinical resistance to trimethoprim might be developing in this clinically important organism. To test this possibility, each documented gene sequence from clinical isolates of P. jirovecii was used to create the recombinant DHFR protein, which was then tested for sensitivity to trimethoprim and other related drugs.
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Why is it important?
Certain variant forms of DHFR tested in our work do show very high resistance to the clinically used drug trimethoprim. No other method currently exists to check for resistance in this organism. Our data would suggest that it would be possible to predict trimethoprim effectiveness by genetic characterization of the DHFR gene in the strain of Pneumocystis infecting an individual patient.
Perspectives
This work required collaboration from a number of individuals and laboratories. All these people came together to approach a problem that was not amenable to solution by other traditional techniques. Pneumocystis cannot be cultured so traditional sensitivity testing is impossible. Our direct approach of creating the target protein coded by the variant genes gave us information on the response of the trimethoprim target in the pathogenic organism.
Sherry Queener
Goodman Campbell Brain and Spine
Read the Original
This page is a summary of: Trimethoprim Resistance of Dihydrofolate Reductase Variants from Clinical Isolates of Pneumocystis jirovecii, Antimicrobial Agents and Chemotherapy, July 2013, ASM Journals,
DOI: 10.1128/aac.01161-13.
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