AUTHOR=Lázaro-Souza Milena , Matte Christine , Lima Jonilson B. , Arango Duque Guillermo , Quintela-Carvalho Graziele , de Carvalho Vivarini Áislan , Moura-Pontes Sara , Figueira Cláudio P. , Jesus-Santos Flávio H. , Gazos Lopes Ulisses , Farias Leonardo P. , Araújo-Santos Théo , Descoteaux Albert , Borges Valéria M. 

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

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00626

DOI=10.3389/fmicb.2018.00626

ISSN=1664-302X

ABSTRACT=<p>Lipophosphoglycan (LPG) is the major surface glycoconjugate of metacyclic <italic>Leishmania</italic> promastigotes and is associated with virulence in various species of this parasite. Here, we generated a LPG-deficient mutant of <italic>Leishmania infantum</italic>, the foremost etiologic agent of visceral leishmaniasis in Brazil. The <italic>L. infantum</italic> LPG-deficient mutant (Δ<italic>lpg1</italic>) was obtained by homologous recombination and complemented via episomal expression of <italic>LPG1</italic> (Δ<italic>lpg1</italic> + <italic>LPG1</italic>). Deletion of <italic>LPG1</italic> 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<italic>lpg1</italic> parasites was delayed. Additionally, the deletion of <italic>LPG1</italic> 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<italic>lpg1</italic> parasites was significantly reduced at 72 h post-infection. Interestingly, <italic>L</italic>. <italic>infantum</italic> LPG-deficient mutants induced a strong NF-κB-dependent activation of the inducible nitric oxide synthase (iNOS) promoter compared to wild type and Δ<italic>lpg1</italic> + <italic>LPG1</italic> parasites. In conclusion, the <italic>L. infantum</italic> Δ<italic>lpg1</italic> mutant constitutes a powerful tool to investigate the role(s) played by LPG in host cell-parasite interactions.</p>