title: Resistance to oxidative stress is associated with metastasis in mucocutaneous leishmaniasis.
abstract: Mucocutaneous leishmaniasis (MCL) in South and Central America is characterized by the dissemination (metastasis) of Leishmania Viannia subgenus parasites from a cutaneous lesion to nasopharyngeal tissues. Little is known about the pathogenesis of MCL, especially with regard to the virulence of the parasites and the process of metastatic dissemination. We previously examined the functional relationship between cytoplasmic peroxiredoxin and metastatic phenotype using highly, infrequently, and nonmetastatic clones isolated from an L. (V.) guyanensis strain previously shown to be highly metastatic in golden hamsters. Distinct forms of cytoplasmic peroxiredoxin were identified and found to be associated with the metastatic phenotype. We report here that peroxidase activity in the presence of hydrogen peroxide and infectivity differs between metastatic and nonmetastatic L. (V.) guyanensis clones. After hydrogen peroxide treatment or heat shock, peroxiredoxin was detected preferentially as dimers in metastatic L. (V.) guyanensis clones and in L. (V.) panamensis strains from patients with MCL, compared with nonmetastatic parasites. These data provide evidence that resistance to the first microbicidal response of the host cell by Leishmania promastigotes is linked to peroxiredoxin conformation and may be relevant to intracellular survival and persistence, which are prerequisites for the development of metastatic disease.
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges, CH-1066 Epalinges, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Acestor
authors.forename: Slavica
authors.initials: S
authors.lastname: Masina
authors.forename: Annette
authors.initials: A
authors.lastname: Ives
authors.forename: John
authors.initials: J
authors.lastname: Walker
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Saravia
authors.forename: Nicolas
authors.initials: N
authors.lastname: Fasel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics*; D007891:Leishmania / Q000235:genetics* / Q000472:pathogenicity*; D007897:Leishmaniasis, Mucocutaneous / Q000469:parasitology* / Q000473:pathology; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009249:NADP / Q000494:pharmacology; D018384:Oxidative Stress; D010544:Peroxidases / Q000235:genetics; D054464:Peroxiredoxins; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000494:pharmacology; D016415:Sequence Alignment; D012720:Severity of Illness Index
chemical_list: D017382:Reactive Oxygen Species; D009249:NADP; D004247:DNA; D010544:Peroxidases; D054464:Peroxiredoxins