Journal of Antimicrobial Chemotherapy (1995) 35, 23-29 Effect of iron chelation on the in-vitro growth of leishmania promastigotes Ketty Soteriadou", Pericles Papavassiliou*, Chryssa Voyiatzaki' and Johan Boelaerr* "Laboratory of Biochemistry, Hellenic Pasteur Institute 11521 Athens, Greece; b Unit of Renal and Infectious Diseases, Algemeen Ziekenhuis Sint-Jan, B-8000 Brugge, Belgium The development of vaccines and drugs to control leishmaniasis is urgently needed. The presence of a leishmania transferrin receptor on the parasite suggests that an adequate supply of iron is needed for the life cycle of leishmania. We have investigated the effect of iron deprivation on the growth of leishmania promastigotes in vitro using an iron chelation approach. All chelators tested reduced the rate of promastigote multiplication in a dose-dependent fashion, whereas referrated ones did not. The hydroxypyridin-4-one chelators CP94 and LI were found to be more efficient than desferrioxamine. We suggest that iron depletion may be an effective mechanism against leishmania infection. Introduction Leishmaniasis is caused by infection with a number of species of the protozoan parasite leishmania, which are transmitted by sandflies. It includes a group of diseases of major health importance, ranging from self-healing cutaneous lesions to severe visceral leishmaniasis or Kala-Azar with a high fatality rate. The distribution of leishmaniasis, often assumed to be a 'tropical disease', is world-wide and the total number of infected people is estimated to be 12 million, the number of new cases of the disease each year being ~l-5 million (Tropical Disease Research, Progress 1991-92). The prevalence of leishmania infection among individuals infected with HIV, as well as the existence of latent asymptomatic infection in endemic areas, may be expected to have important implications for blood banks, iatrogenic immunosuppressive therapy and transplant programmes (Alvar et al., 1992; Aebischer, Moody & Handman, 1993). The emergence of drug resistant parasites, the fact that first-line drugs (antimony compounds) produce side effects and second-line ones (amphotericin B or pentamidine) are toxic, as well as the absence of a vaccine, amply testify to the need for new and more effective drugs. Iron depletion has been proposed as a host defence mechanism against intracellular infection (Weinberg, 1992). Recent data suggest that iron chelation may be an effective chemotherapeutic mechanism against malaria (Hershko et al., 1991; Gordeuk et al, 1992) and a useful adjunct in the therapy of HIV-related infections (Boelaert & Weinberg, 1993). Despite the proven efficacy of desferrioxamine (DFO), a potent iron chelator, in the treatment of iron overload, there is an obvious need to develop alternative, effective, 23 0305-7453/95/010023 + 07 $08.00 © '995 The British Society for Antimicrobial Chemotherapy at University College London on March 7, 2014 http://jac.oxfordjournals.org/ Downloaded from