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Background  Nitric oxide (NO • ) plays a pivotal role as a leishmanicidal agent in mouse macrophages. NO •  resistant  Escherichia coli  and  Mycobacterium tuberculosis  have been associated with a severe outcome of these diseases.    Methods  In this study we evaluated the  in vitro  toxicity of nitric oxide for the promastigote stages of  Leishmania (Viannia) braziliensis  and  Leishmania (Leishmania) amazonensis  parasites, and the infectivity of the amastigote stage for human macrophages. Parasites were isolated from patients with cutaneous, mucosal or disseminated leishmaniasis, and NO •  resistance was correlated with clinical presentation.    Results  Seventeen isolates of  L. (L.) amazonensis  or  L. (V.) braziliensis  promastigotes were killed by up to 8 mM of more of NaNO 2  (pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO 2  were defined as nitric oxide-resistant. Patients infected with nitric oxide-resistant  Leishmania  had significantly larger lesions than patients infected with nitric oxide-susceptible isolates. Furthermore, nitric oxide-resistant  L. (L.) amazonensis  and  L. (V.) braziliensis  multiplied significantly better in human macrophages than nitric oxide-susceptible isolates.    Conclusion  These data suggest that nitric oxide-resistance of  Leishmania  isolates confers a survival benefit for the parasites inside the macrophage, and possibly exacerbates the clinical course of human leishmaniasis.

bmc infectious diseases

Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensisto nitric oxide correlates with disease severity in Tegumentary Leishmaniasis