Leptospira interrogans leptolysin displays proteolytic activity against complement proteins
Carregando...
Data
Data de publicação
Autores IPEN
Orientador
Título da Revista
ISSN da Revista
Título do Volume
É parte de
É parte de
É parte de
Immunobiology
Exportar
Resumo
Pathogenic Leptospira species are extremely efficient in disseminating
in the host, a fact attributed to their ability to escape complement
system activation, and to degrade extracellular matrix and
other components of the human plasma. Recently, our group evaluated
the proteolytic activity of secreted proteins by leptospires,
and exoproteome analyzes of these bacteria allowed the identification
of some proteases, including the metalloprotease pappalysin-1
domain protein, which we named leptolysin. In this work we produced
and functionally characterized leptolysin from L. interrogans
to expand our knowledge on this metalloprotease from Leptospira
in the processes of invasion and immune evasion. According to in
silico analyzes this protease belongs to the category of short pappalysins,
also found in other bacteria. Leptolysin is present in all
Leptospira species but is more conserved among pathogenic species
of the P1 subclade. A preliminary biochemical characterization
of its proteolytic activity was performed using FRET (Free Resonance
Energy Transfer) peptides. The enzyme exhibited maximum
activity at pH 8.0 and 37 C, was active in the presence of different
salts and was strongly inhibited by EDTA and 1,10-phenanthroline.
It showed a marked preference for arginine residues in the P1 position.
The proteolytic activity of recombinant leptolysin on host
molecules was also evaluated in vitro and in vivo. The metalloprotease
was active against extracellular matrix proteins (proteoglycans
and fibronectin), coagulation cascade molecules (fibrinogen
and thrombin) and effector proteins of the human complement
system (C2 to C9). A leptolysin knockout strain (Dlic13434) was
produced and characterized. This strain showed lower survival in
normal human serum (SHN) compared to the wild-type strain.
However, in a model of epicutaneous infection in hamsters, no
attenuation of virulence was observed with the knockout strain,
although the bacterial load in the kidneys of these animals was
lower than that observed in animals inoculated with the wild-type
strain. Finally, data with sera from leptospirosis patients suggest
that leptolysin is produced during natural infections by pathogenic
leptospires. The characterization of toxins, their targets and mechanisms
of action can help in the development of strategies to combat
leptospirosis.
Como referenciar
COURROL, DANIELLA; SILVA, CRISTIANE F. da; CHAMBI, ROSA C.; MORGANTI, LIGIA; ISAAC, LOURDES; PORTARO, FERNANDA; SILVA, RODRIGO R. da; BARBOSA, ANGELA. Leptospira interrogans leptolysin displays proteolytic activity against complement proteins. Immunobiology, v. 228, n. 5, p. 85, 2023. DOI: 10.1016/j.imbio.2023.152651. Disponível em: http://repositorio.ipen.br/handle/123456789/34404. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.