Leishmania (Viannia) braziliensis Inositol Phosphorylceramide: Distinctive Sphingoid Base Composition

Leishmania (Viannia) braziliensis Inositol Phosphorylceramide: Distinctive Sphingoid Base Composition

Author De Castro Levatti, Erica V. Autor UNIFESP Google Scholar
Toledo, Marcos S. Autor UNIFESP Google Scholar
Costa, Renata Watanabe Autor UNIFESP Google Scholar
Bahia, Diana Autor UNIFESP Google Scholar
Mortara, Renato A. Autor UNIFESP Google Scholar
Takahashi, Hello K. Autor UNIFESP Google Scholar
Straus, Anita H. Autor UNIFESP Google Scholar
Abstract Inositol phosphorylceramide (IPC), the major sphingolipid in the genus Leishmania but not found in mammals, is considered a potentially useful target for chemotherapy against leishmaniasis. Leishmania (Viannia) braziliensis is endemic in Latin America and causes American tegumentary leishmaniasis. We demonstrated that IPCs are localized internally in parasites, using a specific monoclonal antibody. Treatment with 5 mu M myriocin (a serine palmitoyltransferase inhibitor) rendered promastigotes 8-fold less infective than controls in experimental hamster infection, as determined by number of parasites per inguinal lymph node after 8 weeks infection, suggesting the importance of parasite IPC or sphingolipid derivatives in parasite infectivity or survival in the host. IPC was isolated from promastigotes of three L. (V.) braziliensis strains and analyzed by positive- and negative-ion ESI-MS. The major IPC ions were characterized as eicosasphinganine and eicosasphingosine. Negative-ion ESI-MS revealed IPC ion species at m/z 778.6 (d20:1/14:0), 780.6 (d20:0/14:0), 796.6 (t20:0/14:0), 806.6 (d20:1/16:0), and 808.6 (d20:0/16:0). IPCs isolated from L. (V) braziliensis and L. (L.) major showed significant differences in IPC ceramide composition. The major IPC ion from L. (L.) major detected in negative-ion ESI-MS at m/z 780.6, was composed of ceramide d16:1/18:0. Our results suggest that sphingosine synthase (also known as serine palmitoyltransferase

SPT) in L. (V.) braziliensis is responsible for synthesis of a long chain base of 20 carbons (d20), whereas SPT in L. (L.) major synthesizes a 16-carbon long-chain base (d16). A phylogenetic tree based on SPT proteins was constructed by analysis of sequence homologies in species of the Leishmania and Viannia subgenera. Results indicate that SPT gene position in L. (V) braziliensis is completely separated from that of members of subgenus Leishmania, including L. (L.) major L. (L.) infantum, and L. (L.) mexicana. Our findings clearly demonstrate sphingoid base differences between L. (V) braziliensis and members of subgenus Leishmania, and are relevant to future development of more effective targeted anti leishmaniasis drugs.
Keywords antibody
ceramide
phosphoinositide
mass spectrometry
sphingolipid
eicosasphinganine
eicosasphingosine
Language English
Sponsor Fundação de Amparo a Pesquisa do Estado de São Paulo
Conselho Nacional de Desenvolvimen to Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2006/07005-4
CNPq: 486491/2012-9
CNPq: 307209/2015-6
Date 2017
Published in Frontiers In Microbiology. Lausanne, v. 8, p. -, 2017.
ISSN 1664-302X (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fmicb.2017.01453
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000406946000001
URI http://repositorio.unifesp.br/handle/11600/51398

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