Leishmania chagasi naturally resistant to nitric oxide isolated from humans and dogs with visceral leishmaniasis in Brazil

Abstract

Nitric oxide (NO) plays an important role as a leishmanicidal agent in murine macrophages. NO resistant Escherichia coli and Mycobacterium tuberculosis have been associated with poor outcomes of their resulting diseases. NO resistant Leishmania braziliensis has also been identified and exacerbates the clinical course of human leishmaniasis. We report, for the first time, natural resistance of Leishmania chagasi promastigotes to NO. These parasites were isolated from humans and dogs with visceral leishmaniasis. We also demonstrate that this resistance profile was associated with a greater survival capacity and a greater parasite burden in murine macrophages, independent of activation and after activation by IFN-γ and LPS.

Expression of glyceraldehyde 3-phosphate dehydrogenase is enhanced in Leishmania spp naturally resistant to nitric oxide

“…The NO-resistance of these L. infantum promastigotes was induced in vitro by increasing NO donor pressure in a stepwise fashion. Natural resistance to NO was also demonstrated to occur in L. amazonensis (Giudice et al, 2007) and L. chagasi (Santos et al, 2012). Here, we demonstrate a slight increase in the GAPDH activity in such an L. amazonensis isolate naturally resistant to NO, which became sharper when the parasites were exposed to NaNO 2 (16 mM) for two hours.…”

“…These parasites were isolated from humans and dogs with visceral leishmaniasis and its resistance profile was associated with a greater survival capacity and a greater parasite burden in murine macrophages (Santos et al, 2012).…”

Induction, Propagation, and Activity of Host Nitric Oxide: Lessons from Leishmania Infection

“…However, no such studies were performed with Leishmania infection. The role of NO production on the course of Leishmania infection in humans has been addressed mostly indirectly, for instance, by correlating parasite susceptibility to NO and disease severity in patients [75][76][77]. Understanding the factors regulating NO production and bioavailability in humans may be of particular interest for the development of new therapeutic strategies.…”

“…For instance, parasites isolated from certain patients infected with L. amazonensis, L. braziliensis, and L. chagasi exhibited an increased resistance to NO in culture [75][76][77]. Interestingly, these patients responded poorly to standard antimonial treatments, suggesting that antimonial antileishmanial drugs may act in part by promoting NO production and antimicrobial activity in infected lesions.…”

In vitro infection by Leishmania infantum in the peripheral blood mononuclear cell-derived macrophages from crab-eating foxes ( Cerdocyon thous )

“…Following isolation, parasite isolates were cryopreserved. The strain used in this experiment (MCAN/BR/2010/LVC30) was previously characterized by Santos et al (2012) and was shown to be resistant to nitric oxide. Prior to infection, the promastigotes were expanded in Schneider's insect medium (Sigma Chemical Co., St. Louis, MO, USA) pH 7.2 supplemented with 10% heat-inactivated fetal bovine serum (FBS) and 100 U/ml of penicillin/streptomycin.…”