Leishmania infantum Lipophosphoglycan-Deficient Mutants: A Tool to Study Host Cell-Parasite Interplay.

Autor: Lázaro-Souza M; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil.; Department of Legal Medicine, Federal University of Bahia, Salvador, Brazil., Matte C; Institut National de la Recherche Scientifique -Institut Armand-Frappier, Laval, QC, Canada., Lima JB; Center of Biological Sciences and Health, Federal University of Western of Bahia, Barreiras, Brazil., Arango Duque G; Institut National de la Recherche Scientifique -Institut Armand-Frappier, Laval, QC, Canada., Quintela-Carvalho G; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil.; Department of Legal Medicine, Federal University of Bahia, Salvador, Brazil.; Instituto Federal de Educação, Ciência e Tecnologia Baiano (IFBaiano), Alagoinhas, Brazil., de Carvalho Vivarini Á; Laboratory of Molecular Parasitology, Carlos Chagas Filho Biophysics Institute, Center of Health Science, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Moura-Pontes S; Department of Legal Medicine, Federal University of Bahia, Salvador, Brazil., Figueira CP; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil., Jesus-Santos FH; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil.; Department of Legal Medicine, Federal University of Bahia, Salvador, Brazil., Gazos Lopes U; Laboratory of Molecular Parasitology, Carlos Chagas Filho Biophysics Institute, Center of Health Science, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Farias LP; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil., Araújo-Santos T; Center of Biological Sciences and Health, Federal University of Western of Bahia, Barreiras, Brazil., Descoteaux A; Institut National de la Recherche Scientifique -Institut Armand-Frappier, Laval, QC, Canada., Borges VM; Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institut, Oswaldo Cruz Foundation, Salvador, Brazil.; Department of Legal Medicine, Federal University of Bahia, Salvador, Brazil.
Jazyk: angličtina
Zdroj: Frontiers in microbiology [Front Microbiol] 2018 Apr 05; Vol. 9, pp. 626. Date of Electronic Publication: 2018 Apr 05 (Print Publication: 2018).
DOI: 10.3389/fmicb.2018.00626
Abstrakt: Lipophosphoglycan (LPG) is the major surface glycoconjugate of metacyclic Leishmania promastigotes and is associated with virulence in various species of this parasite. Here, we generated a LPG-deficient mutant of Leishmania infantum , the foremost etiologic agent of visceral leishmaniasis in Brazil. The L. infantum LPG-deficient mutant (Δ lpg1 ) was obtained by homologous recombination and complemented via episomal expression of LPG1 (Δ lpg1 + LPG1 ). Deletion of LPG1 had no observable effect on parasite morphology or on the presence of subcellular organelles, such as lipid droplets. While both wild-type and add-back parasites reached late phase in axenic cultures, the growth of Δ lpg1 parasites was delayed. Additionally, the deletion of LPG1 impaired the outcome of infection in murine bone marrow-derived macrophages. Although no significant differences were observed in parasite load after 4 h of infection, survival of Δ lpg1 parasites was significantly reduced at 72 h post-infection. Interestingly, L . infantum LPG-deficient mutants induced a strong NF-κB-dependent activation of the inducible nitric oxide synthase (iNOS) promoter compared to wild type and Δ lpg1 + LPG1 parasites. In conclusion, the L. infantum Δ lpg1 mutant constitutes a powerful tool to investigate the role(s) played by LPG in host cell-parasite interactions.
Databáze: MEDLINE