Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient

Autor(es):Mostrar menos -

Alves-Ferreira, Eliza V. C. ^[1] ; Toledo, Juliano S. ^{[1, 2]} ; De Oliveira, Arthur H. C. ^{[3, 1]} ; Ferreira, Tiago R. ^[1] ; Ruy, Patricia C. ^[1] ; Pinzan, Camila F. ^[1] ; Santos, Ramon F. ^[1] ; Boaventura, Viviane ^{[4, 5]} ; Rojo, David ^[2] ; Lopez-Gonzalvez, Angelez ^[2] ; Rosa, Jose C. ^[1] ; Barbas, Coral ^[2] ; Barral-Netto, Manoel ^{[4, 5]} ; Barral, Aldina ^{[4, 5]} ; Cruz, Angela K. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Biol Celular & Mol & Bioagentes Patogen, Fac Med Ribeirao Preto, Sao Paulo - Brazil

^[2] Univ CEU San Pablo, Ctr Metabol & Bioanal CEMBIO, Interacc & Bioanal UMIB, Madrid - Spain

^[3] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Preto, Sao Paulo - Brazil

^[4] Fdn Oswaldo Cruz FIOCRUZ, Ctr Pesquisas Goncalo Moniz CPqGM, Salvador, BA - Brazil

^[5] Univ Fed Bahia, Fac Med, Salvador, BA - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 9, n. 9 SEP 2015.
• Citações Web of Science: 16

Resumo

Background Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in similar to 10% of L. braziliensis-infected patients. Thus, clinical isolates from patients with CL and MCL may be a relevant source of information to uncover parasite factors contributing to pathogenesis. In this study, we investigated two pairs of L. (V.) braziliensis isolates from mucosal (LbrM) and cutaneous (LbrC) sites of the same patient to identify factors distinguishing parasites that migrate from those that remain at the primary site of infection. Methodology/Principal Findings We observed no major genomic divergences among the clinical isolates by molecular karyotype and genomic sequencing. RT-PCR revealed that the isolates lacked Leishmania RNA virus (LRV). However, the isolates exhibited distinct in vivo pathogenesis in BALB/c mice; the LbrC isolates were more virulent than the LbrM isolates. Metabolomic analysis revealed significantly increased levels of 14 metabolites in LbrC parasites and 31 metabolites in LbrM parasites that were mainly related to inflammation and chemotaxis. A proteome comparative analysis revealed the overexpression of LbrPGF2S (prostaglandin f2-alpha synthase) and HSP70 in both LbrC isolates. Overexpression of LbrPGF2S in LbrC and LbrM promastigotes led to an increase in infected macrophages and the number of amastigotes per cell at 24-48 h post-infection (p.i.). Conclusions/Significance Despite sharing high similarity at the genome structure and ploidy levels, the parasites exhibited divergent expressed genomes. The proteome and metabolome results indicated differential profiles between the cutaneous and mucosal isolates, primarily related to inflammation and chemotaxis. BALB/c infection revealed that the cutaneous isolates were more virulent than the mucosal parasites. Furthermore, our data suggest that the LbrPGF2S protein is a candidate to contribute to parasite virulence profiles in the mammalian host. (AU)

• Processo FAPESP: 11/02040-4 - Investigação do papel da Prostaglandina F2-alfa sintase na interação entre Leishmania braziliensis e hospedeiro
• Beneficiário: Eliza Vanessa Carneiro Alves Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/20597-3 - Investigação da interação parasito-hospedeiro: explorando modelos de estudo de virulência e tropismo
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/01641-4 - Comparação do genoma expresso de isolados de Leishmania braziliensis responsáveis por manifestações clínicas distintas
• Beneficiário: Eliza Vanessa Carneiro Alves Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 06/50323-7 - Estudo do controle da expressão gênica e plasticidade genética em Leishmania
• Beneficiário: Angela Kaysel Cruz
• Modalidade de apoio: Auxílio à Pesquisa - Temático