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Resistance of Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis
Journal article   Open access   Peer reviewed

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

Angela Giudice, Ilza Camada, Paulo TG Leopoldo, Júlia MB Pereira, Lee W Riley, Mary E Wilson, John L Ho, Amelia Ribeiro de Jesus, Edgar M Carvalho and Roque P Almeida
BMC infectious diseases, Vol.7(1), pp.7-7
2007
DOI: 10.1186/1471-2334-7-7
PMID: 17316450
url
https://doi.org/10.1186/1471-2334-7-7View
Published (Version of record) Open Access

Abstract

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 NaNO2 (pH 5.0) and therefore were defined as nitric oxide-susceptible. In contrast, eleven isolates that survived exposure to 16 mM NaNO2 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.

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