Inducible resistance to oxidant stress in the protozoan Leishmania chagasi

Leishmania sp, protozoa are introduced into a mammalian skin by a sandfly v ector, whereupon they en counter increased temperature and toxic oxidants g enerated during phagocytosis, We studied the effects of 37 degreesC "heat s hock" or sublethal menadione, which generates superoxide and hydrogen perox ide, on Leishmania chagasi virulence. Both heat and menadione caused parasi tes to become more resistant to H2O2-mediated toxicity. Peroxide resistance was also induced as promastigotes developed in culture from logarithmic to their virulent stationary phase form. Peroxide resistance was not associat ed with an increase in reduced thiols (trypanothione and glutathione) or in creased activity of ornithine decarboxylase, which is rate-limiting in tryp anothione synthesis. Membrane lipophosphoglycan increased in size as parasi tes developed to stationary phase but not after environmental exposures. In stead, parasites underwent a heat shock response upon exposure to heat or s ublethal menadione, detected by increased levels of HSP70. Transfection of promastigotes with L, chagasi HSP70 caused a heat inducible increase in res istance to peroxide, implying it is involved in antioxidant defense. We con clude that leishmania have redundant mechanisms for resisting toxic oxidant s, Some are induced during developmental change and others are induced in r esponse to environmental stress.