Role of Aquaglyceroporin (AQP1) Gene and Drug Uptake in Antimony-resistant Clinical Isolates of Leishmania donovani

Mahendra Maharjan School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India

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Sushma Singh School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India

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Mitali Chatterjee School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India

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Rentala Madhubala School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India

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Antimonial-containing drugs are the first line of treatment against Leishmaniasis. Resistance to antimonials in Leishmania is proposed to be due to reduced uptake of trivalent antimony (SbIII) through the aquaglyceroporin (AQP1). We investigated the uptake of SbIII and involvement of aquaglyceroporin in developing antimony resistance phenotype in Leishmania donovani clinical isolates. SbIII accumulation, copy number of AQP1 gene, and transcript levels were compared in antimony-sensitive versus -resistant isolates. Antimony-resistant field isolates showed reduced uptake of SbIII. The copy number of AQP1 gene showed higher copy number in the antimony-resistant isolates when compared with the sensitive isolates and did not correlate to the reduced uptake of SbIII. Downregulation of AQP1 RNA levels was not consistently found in the antimony-resistant isolates. Our studies indicate that while downregulation of AQP1 may be one of the mechanisms of antimony resistance, it is however not an invariable feature.

Author Notes

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