Please use this identifier to cite or link to this item: http://www.arca.fiocruz.br/handle/icict/13443
Title: Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient.
Authors: Ferreira, Eliza V. C. Alves
Toledo, Juliano Simões de
Oliveira, Arthur H. C. De
Ferreira, Tiago Rodrigues
Ruy, Patricia C
Pinzan, Camila F
Santos, Ramon de Freitas
Oliveira, Viviane Sampaio Boaventura
Rojo, David
Gonzálvez, Ángelez López
Rosa, Jose César
Barbas, Coral
Barral Netto, Manoel
Barral, Aldina Maria Prado
Cruz, Angela Kaysel
Affilliation: Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil / Universidad CEU San Pablo. Centro de Metabolómica y Bioanálisis (CEMBIO). Interacciones y Bioanálisis (UMIB). Boadilla del Monte, Madrid, Spain
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil / Universidade de São Paulo. Faculdade de Filosofia, Ciências e Letras de Ribeirão PretoRibeirão Preto. Departamento de Química. São Paulo, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Universidad CEU San Pablo. Centro de Metabolómica y Bioanálisis (CEMBIO). Interacciones y Bioanálisis (UMIB). Boadilla del Monte, Madrid, Spain
Universidad CEU San Pablo. Centro de Metabolómica y Bioanálisis (CEMBIO). Interacciones y Bioanálisis (UMIB). Boadilla del Monte, Madrid, Spain
Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos. Ribeirão Preto, SP, Brasil
Universidad CEU San Pablo. Centro de Metabolómica y Bioanálisis (CEMBIO). Interacciones y Bioanálisis (UMIB). Boadilla del Monte, Madrid, Spain
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil
Abstract: 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 ~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.
keywords: Leishmania braziliensis
Leishmaniose
Genética
Macrófagos
Animal
Ratos
Infecção
Issue Date: 2015
Publisher: Public Library of Science
Citation: FERREIRA, E. V. C. A. et al. Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient. PLoS Neglected Tropical Diseases, v. 9, n. 9, p. e0004018, 2015.
DOI: 10.1371/journal.pntd.0004018
ISSN: 1935-2727
Copyright: open access
Appears in Collections:IGM - Artigos de Periódicos

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