Generation of an aquaglyceroporin AQP1 null mutant in Leishmania major

Mol Biochem Parasitol. 2015 Jun;201(2):108-11. doi: 10.1016/j.molbiopara.2015.07.003. Epub 2015 Jul 26.


The Leishmania aquaglyceroporin AQP1 plays an important physiological role in water and uncharged polar solutes transport, volume regulation, osmotaxis, and is a key determinant of antimony resistance. By targeted gene disruption, we generated a Leishmania major promastigote AQP1 null mutant. This required several attempts but a chromosomal null AQP1 mutant was obtained by loss of heterozygosity in the presence of a rescue plasmid encoding AQP1. Growth in the absence of selection led to the loss of the rescuing plasmid, indicating that AQP1 is not essential for Leishmania viability. The AQP1-null mutant was resistant to antimonyl tartrate (SbIII) and arsenite (AsIII) due to a decrease import of these metalloids. It also exhibited alterations in its osmoregulation abilities compared with wild-type cells. This is the first report of the generation of a genetic AQP1 null mutant in Leishmania parasite, confirming its physiological function and role in resistance to antimonials, the therapeutic mainstay against Leishmania.

Keywords: Antimony resistance; Aquaglyceroporin AQP1; Leishmania; Osmoregulation; Transport assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimony Potassium Tartrate / toxicity
  • Aquaglyceroporins / deficiency*
  • Arsenites / toxicity
  • Cell Survival / drug effects
  • Drug Resistance
  • Gene Knockout Techniques*
  • Leishmania major / drug effects
  • Leishmania major / genetics*
  • Leishmania major / physiology
  • Osmoregulation


  • Aquaglyceroporins
  • Arsenites
  • Antimony Potassium Tartrate