PROSPECTING TICK SIALOMES FOR DISCOVERY OF NEW ANTIMICROBIAL COMPONENTS

• Grant number: 13/00382-0
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): June 01, 2013
• Effective date (End): April 30, 2016
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal researcher: Isabel Kinney Ferreira de Miranda Santos
• Grantee: Gustavo Rocha Garcia
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Tick salivary glands contain many molecules with potential applications as new antimicrobials, which are urgently needed. We generated a fully annotated transcriptome, obtained with 454 sequencing technology, for salivary glands of various developmental stages of Rhipicephalus microplus, the cattle tick. A corresponding proteome was constructed with MudPIT. In these we found many coding sequences and peptides for putative secreted antimicrobial peptides (AMPs). The AMPs are distributed in several families, each with several members: defensins, hebrains, Trypsin inhibitor-like-TIL domain containing AMPs, longicornisin and a family with intermediate similarities to neutrophil elastase inhibitors and AMPs. Pathogen recognition proteins such as ficolin and lipid interacting ML domains were also identified. Nothing is known about the biological activity of these putative AMPs and how they compare with each other in antimicrobial potency and specificity. In order to identify new antimicrobials we will synthesize peptides guided by >80 coding full length sequences containing signal peptides that were bioinformatically mined from the transcriptome of salivary glands of R. microplus. In the case of larger TIL-domain proteins, we will express recombinant proteins. These peptides and proteins will be tested in standard assays of inhibition of microbial growth in order to determine their minimum inhibitory concentrations. They will also be tested in standard assays of stability under ranges of temperatures and pH. Toxicity for mammalian hosts will be initially assessed by means of standard lytic assays for red blood cells. Peptides will synthesized by service contracts. We expect to identify several candidate AMPs for development as new antimicrobials. Keywords: Antimicrobial peptides (AMP), Saliva; Ticks; Rhipicephalus microplus.

Scientific publications

(7)

(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)

GARCIA, GUSTAVO ROCHA; MARUYAMA, SANDRA REGINA; NELSON, KRISTINA T.; CHAVES RIBEIRO, JOSE MARCOS; GARDINASSI, LUIZ GUSTAVO; MENDES MAIA, ANTONIO AUGUSTO; FERREIRA, BEATRIZ ROSSETTI; KOOYMAN, FRANS N. J.; DE MIRANDA SANTOS, ISABEL K. F.. Immune recognition of salivary proteins from the cattle tick Rhipicephalus microplus differs according to the genotype of the bovine host. PARASITES & VECTORS, v. 10, MAR 14 2017. (12/15464-0, 12/04087-0, 13/00382-0)

MAGALHAES, LIZANDRA G.; LIMA, THAIS C.; DE PAULA, RENATO G.; MORAIS, ENYARA R.; AGUIAR, DANIELA P.; GARDINASSI, LUIZ G.; GARCIA, GUSTAVO R.; LAURENTIZ, ROSANGELA S.; RODRIGUES, VANDERLEI; BASTOS, JAIRO K.; et al. Effects of (-)-6,6 `-dinitrohinokinin on adult worms of Schistosoma mansoni: a proteomic analyses. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 26, n. 3, p. 334-341, MAY-JUN 2016. (10/17378-8, 09/15207-4, 13/00382-0)

GARDINASSI, LUIZ GUSTAVO; DESOUZA-VIEIRA, THIAGO S.; DA SILVA, NAILA O.; GARCIA, GUSTAVO R.; BORGES, VALERIA M.; CAMPOS, ROSEANE N. S.; DE ALMEIDA, ROQUE P.; DE MIRANDA SANTOS, ISABEL K. F.; SARAIVA, ELVIRA M.. Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis. PARASITES & VECTORS, v. 10, JUN 6 2017. (14/25856-8, 11/23819-0, 13/00382-0)

GARCIA, GUSTAVO R.; RIBEIRO, JOSE MARCOS CHAVES; MARUYAMA, SANDRA REGINA; GARDINASSI, LUIZ GUSTAVO; NELSON, KRISTINA; FERREIRA, BEATRIZ R.; ANDRADE, THALES GALDINO; FERREIRA DE MIRANDA SANTOS, ISABEL K.. A transcriptome and proteome of the tick Rhipicephalus microplus shaped by the genetic composition of its hosts and developmental stage. SCIENTIFIC REPORTS, v. 10, n. 1, JUL 30 2020. (12/04087-0, 13/00382-0)

GARDINASSI, LUIZ GUSTAVO; GARCIA, GUSTAVO ROCHA; NERY COSTA, CARLOS HENRIQUE; SILVA, VLADIMIR COSTA; FERREIRA DE MIRANDA SANTOS, ISABEL KINNEY. Blood Transcriptional Profiling Reveals Immunological Signatures of Distinct States of Infection of Humans with Leishmania infantum. PLoS Neglected Tropical Diseases, v. 10, n. 11, NOV 2016. (13/00382-0, 11/23819-0, 14/25856-8, 12/06708-2)

GARDINASSI, LUIZ GUSTAVO; DOTZ, VIKTORIA; EDERVEEN, AGNES HIPGRAVE; DE ALMEIDA, ROQUE PACHECO; NERY COSTA, CARLOS HENRIQUE; COSTA, DORCAS LAMOUNIER; DE JESUS, AMELIA RIBEIRO; MAYBORODA, OLEG A.; GARCIA, GUSTAVO ROCHA; WUHRER, MANFRED; et al. Clinical Severity of Visceral Leishmaniasis Is Associated with Changes in Immunoglobulin G Fc N-Glycosylation. MBIO, v. 5, n. 6, NOV-DEC 2014. (12/06708-2, 11/23819-0, 13/00382-0)

LIZANDRA G. MAGALHÃES; THAIS C. LIMA; RENATO G. DE PAULA; ENYARA R. MORAIS; DANIELA P. AGUIAR; LUIZ G. GARDINASSI; GUSTAVO R. GARCIA; ROSANGELA S. LAURENTIZ; VANDERLEI RODRIGUES; JAIRO K. BASTOS; et al. Effects of (-)-6,6'-dinitrohinokinin on adult worms of Schistosoma mansoni: a proteomic analyses. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 26, n. 3, p. 334-341, 2016-06-00. (09/15207-4, 13/00382-0, 10/17378-8)