Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress.
The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0-kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work, we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L. amazonensis promastigotes. Leishmania META2-null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. By contrast, META2 expression is decreased by 80% in RNAi-induced T. brucei bloodstream forms with no measurable effect on survival or resistance to heat shock.
Ramos
Camila S
CS
Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, USP, São Paulo, Brazil.
Yokoyama-Yasunaka
Jenicer K U
JK
Guerra-Giraldez
Cristina
C
Price
Helen P
HP
Mortara
Renato A
RA
Smith
Deborah F
DF
Uliana
Silvia R B
SR
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006358:Hot Temperature / Q000009:adverse effects*; D007894:Leishmania mexicana / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016773:Leishmaniasis, Cutaneous / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009154:Mutation; D009675:Novobiocin / Q000494:pharmacology; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D018384:Oxidative Stress; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism
D000981:Antiprotozoal Agents; D019384:Nucleic Acid Synthesis Inhibitors; D009942:Organometallic Compounds; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D009675:Novobiocin; D008536:Meglumine; D000077485:Meglumine Antimoniate