Production and characterization of the protease pappalysin from Leptospira interrogans

• Grant number: 19/22706-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2020
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Angela Silva Barbosa
• Grantee: Daniella dos Santos Courrol
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Pathogenic Leptospira species are extremely efficient in disseminating in the host, a fact attributed to their ability to escape complement system activation - the first line of defense of the innate immune response - and also to the ability to degrade extracellular matrix and other components of the human plasma. The secretion of proteases that inactivate host proteins is an important tool used by various microorganisms during the colonization process. The mechanisms underlying tissue damage caused by pathogenic leptospires are still poorly understood. Like other bacteria, leptospires cross epithelial and endothelial barriers to gain access to organs. Adhesion and degradation of extracellular matrix components, especially the basement membrane, are certainly required for invasion. Recently, our group evaluated the proteolytic activity of proteins present in the culture supernatant of two Leptospira strains, one pathogenic (virulent) and another saprophyte. The results showed that proteases present only in the supernatant of the virulent strain were able to degrade proteoglycans, fibrinogen and plasma fibronectin. Furthermore, an analysis of the exoproteome of a virulent strain allowed the identification of some proteases, among which the metalloprotease "pappalysin-1 domain protein" (papalisin) (EKO25673.1). The objective of this project is to produce and functionally characterize L. interrogans papalisin in order to increase our knowledge about these Leptospira metalloproteases in the invasion and immune evasion processes. (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)

COURROL, DANIELLA DOS SANTOS; DA SILVA, CRISTIANE CASTILHO FERNANDES; PRADO, LUAN GAVIAO; CHURA-CHAMBI, ROSA MARIA; MORGANTI, LIGIA; DE SOUZA, GISELE OLIVEIRA; HEINEMANN, MARCOS BRYAN; ISAAC, LOURDES; CONTE, FERNANDO PAIVA; VIEIRA PORTARO, FERNANDA CALHETA; et al. Leptolysin, a Leptospira secreted metalloprotease of the pappalysin family with broad-spectrum activity. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 20-pg., 2022-08-23. (18/12896-2, 19/22706-9, 17/12924-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COURROL, Daniella dos Santos. Production and characterization of the protease pappalysin from Leptospira interrogans. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.