The BpeEF-OprC Efflux Pump Is Responsible for Widespread Trimethoprim Resistance in Clinical and Environmental Burkholderia pseudomallei Isolates

<jats:title>ABSTRACT</jats:title><jats:p>Trimethoprim-sulfamethoxazole (co-trimoxazole) is the primary drug used for oral eradication therapy of<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Burkholderia pseudomallei</jats:named-content>infections (melioidosis). Here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast Thailand and northern Australia. This resistance was shown to be due to BpeEF-OprC efflux pump expression. No dihydrofolate reductase target mutations were involved, although frequent insertion of IS<jats:italic>Bma</jats:italic>2 was noted within the putative<jats:italic>folA</jats:italic>transcriptional terminator. All isolates tested remained susceptible to trimethoprim-sulfamethoxazole, suggesting that resistance to trimethoprim alone in these strains probably does not affect the efficacy of co-trimoxazole therapy.</jats:p>