Banca de QUALIFICAÇÃO: MARIA BÁRBARA SILVA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MARIA BÁRBARA SILVA
DATE: 31/12/2025
TIME: 09:00
LOCAL: videoconferencia
TITLE:

MECHANISMS OF COMPLEMENT SYSTEM ACTIVATION INDUCED BY PROTOZOAN VIRULENCE FACTORS: AN EXPLORATORY STUDY MODEL

KEY WORDS:

Trypanosomatidae; Metalloproteases; Complement system; Neuraminidase; Parasite virulence

PAGES: 90
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Protozoa of the family Trypanosomatidae, such as species of the genera Leishmania and Trypanosoma cruzi, are the etiological agents of leishmaniasis and Chagas disease, also known as American trypanosomiasis. These diseases occur predominantly in tropical and subtropical regions, especially in areas marked by poverty.Leishmaniasis is an infectious disease that can present in different clinical forms, including cutaneous leishmaniasis (localized or diffuse), mucocutaneous leishmaniasis, and visceral leishmaniasis. In contrast, Chagas disease primarily manifests as an inflammatory cardiomyopathy. A characteristic feature of trypanosomatids is the presence of metalloproteases, which play important roles in parasite virulence, in the development of the infections they cause, and in evasion of the host immune responses mediated by the complement system. In this context, a deeper understanding of the interactions between these agents and the vertebrate host is required. Accordingly, the present study aimed to biochemically and biologically characterize metalloproteases—enzymes common to trypanosomatids—involved in the virulence processes of these clinically important protozoa. In addition, the metalloprotease profile in human erythrocytes (HE) was evaluated, as well as the interaction of neuraminidase-sensitized erythrocytes, in order to assess complement-mediated hemolytic activity. To this end, electrophoretic and enzymatic profiles were analyzed for promastigote forms of L. infantum, as well as epimastigote and trypomastigote forms of the Y strain of T. cruzi, in addition to human erythrocytes at different concentrations (1%, 1.5%, 2%, 2.5%, 5%, and 10%). To evaluate complement-mediated lysis, erythrocytes at 2% were treated with different concentrations of neuraminidase (0 U/mL; 0.001 U/mL; 0.01 U/mL; 0.1 U/mL; and 0.5 U/mL) and then exposed to active and inactive complement systems. All obtained profiles exhibited enzymatic activity, revealing distinct protein and zymographic patterns. In Leishmania spp. extracts, the expression of enzymes with molecular masses between 50 and 80 kDa was observed, possibly corresponding to the 63 kDa glycoprotein (gp63). In T. cruzi extracts, the expression of enzymes of approximately 35 and 48 kDa was detected. The results of complement-mediated lysis indicate that neuraminidase increases cell lysis in a concentration-dependent manner only in the presence of active complement, whereas low or no hemolytic activity is observed in the presence of inactive complement.

COMMITTEE MEMBERS:
Externa ao Programa - 1143827 - JULIANA FELIX DA SILVA - nullExterna ao Programa - 3471472 - JULIANE SANTOS DE FRANÇA DA SILVA - nullPresidente - 2213126 - VALTER FERREIRA DE ANDRADE NETO