Visceral leishmaniasis: genomics approaches for integrated molecular analysis of host and parasite

• Grant number: 16/20258-0
• Support type: Research Grants - Young Investigators Grants
• Duration: July 01, 2017 - October 31, 2022
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Sandra Regina Costa Maruyama
• Grantee: Sandra Regina Costa Maruyama
• Home Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Assoc. researchers: Anderson Ferreira da Cunha ; Iran Malavazi ; João Santana da Silva
• Associated scholarship(s): 19/24764-6 - Tools for nucleic acid manipulation in samples of visceral leishmaniasis, BP.TT; 19/07718-0 - Tools for nucleic acid manipulation in samples of visceral leishmaniasis., BP.TT; 19/03095-9 - Screening of clinical isolates of Leishmania sp. for genome sequencing, BP.MS; + associated scholarships 18/26799-9 - Phenotypic characterization and genomic analysis of Crithidia-like parasites obtained from patients diagnosed with visceral leishmaniasis., BP.MS; 18/05767-1 - Tools for nucleic acid manipulation in samples of Visceral Leishmaniasis, BP.TT; 17/16328-6 - Visceral Leishmaniasis: genomics approaches for integrated molecular analysis of host and parasite., BP.JP - associated scholarships

Abstract

Visceral leishmaniasis (VL) in Brazil is caused by protozoan parasites Leishmania infantum. It is a chronic and disseminated disease that can be potentially fatal if untreated. Interestingly, most people infected are asymptomatic, whereas approximately 15% of L. infantum infections develop clinical manifestations, which range from mild to severe forms of disease. Both host immune responses and the genetics of parasites are crucial to the outcome of infection; however the molecular mechanisms involved in the pathogenesis of VL remain poorly understood. We believe that molecular analyses of leukocytes from asymptomatic individuals (resistants to VL), diseased and cured patients, as well as the genomic analyses of clinical isolates will provide insightful information to elucidate the molecular mechanisms of parasite/host interaction that underlie the outcome of infection. Thus, the aim of this proposal is performing an integrated molecular analysis of VL through the Functional Genomics of host (whole blood RNA-seq) and the Comparative Genomics of parasites (WGS, whole-genome sequencing) for data integration that can be helpful to discovery of novel targets for therapies and drugs. Our preliminary results on RNA-seq analyses of blood leukocytes from VL patients and WGS of Leishmania clinical isolates reveal that this is an innovative and promising research proposal. Through the RNA-seq analyses of symptomatic infected patients before (diseased patients) and after (cured patients) of being submitted to the conventional treatment, asymptomatic patients and healthy control individuals, the gene signatures related to VL will be identified. The dual RNA-seq of patient samples will identify Leishmania transcripts. Also, a protocol for RNA-seq of whole blood stimulation will be developed. Comparative Genomics analyses of clinical isolates will determine ploidy, chromosome somy, copy number variations (CNVs) and single-nucleotide polymorphisms (SNPs) and genes or genomic regions associated to resistance to conventional drugs, beyond the valuable biological information about Brazilian strains of parasites. Finally, according to the purpose of FAPESP Young Investigator Award, this proposal aims to establish a novel research area (Genomics of host/parasite interaction in leishmaniasis) at the Department of Genetics and Evolution of the Federal University of São Carlos. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARUYAMA, SANDRA R.; DE SANTANA, ALYNNE K. M.; TAKAMIYA, NAYORE T.; TAKAHASHI, TALITA Y.; ROGERIO, LUANA A.; OLIVEIRA, CAIO A. B.; MILANEZI, CRISTIANE M.; TROMBELA, VIVIANE A.; CRUZ, ANGELA K.; JESUS, AMELIA R.; BARRETO, ALINE S.; DA SILVA, ANGELA M.; ALMEIDA, ROQUE P.; RIBEIRO, JOSE M.; SILVA, JOAO S. Non-Leishmania Parasite in Fatal Visceral Leishmaniasis Like Disease, Brazil. Emerging Infectious Diseases, v. 25, n. 11, p. 2088-2092, NOV 2019. Web of Science Citations: 1.