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.
journal_name
BMC Infect Disjournal_title
BMC infectious diseasesauthors
Giudice A,Camada I,Leopoldo PT,Pereira JM,Riley LW,Wilson ME,Ho JL,de Jesus AR,Carvalho EM,Almeida RPdoi
10.1186/1471-2334-7-7subject
Has Abstractpub_date
2007-02-22 00:00:00pages
7issn
1471-2334pii
1471-2334-7-7journal_volume
7pub_type
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