title: Plasminogen binding proteins and plasmin generation on the surface of Leptospira spp.: the contribution to the bacteria-host interactions.
abstract: Leptospirosis is considered a neglected infectious disease of human and veterinary concern. Although extensive investigations on host-pathogen interactions have been pursued by several research groups, mechanisms of infection, invasion and persistence of pathogenic Leptospira spp. remain to be elucidated. We have reported the ability of leptospires to bind human plasminogen (PLG) and to generate enzimatically active plasmin (PLA) on the bacteria surface. PLA-coated Leptospira can degrade immobilized ECM molecules, an activity with implications in host tissue penetration. Moreover, we have identified and characterized several proteins that may act as PLG-binding receptors, each of them competent to generate active plasmin. The PLA activity associated to the outer surface of Leptospira could hamper the host immune attack by conferring the bacteria some benefit during infection. The PLA-coated leptospires obstruct complement C3b and IgG depositions on the bacterial surface, most probably through degradation. The decrease of leptospiral opsonization might be an important aspect of the immune evasion strategy. We believe that the presence of PLA on the leptospiral surface may (i) facilitate host tissue penetration, (ii) help the bacteria to evade the immune system and, as a consequence, (iii) permit Leptospira to reach secondary sites of infection.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Vieira
authors.forename: Marina V
authors.initials: MV
authors.lastname: Atzingen
authors.forename: Rosane
authors.initials: R
authors.lastname: Oliveira
authors.forename: Renata S
authors.initials: RS
authors.lastname: Mendes
authors.forename: Renan F
authors.initials: RF
authors.lastname: Domingos
authors.forename: Silvio A
authors.initials: SA
authors.lastname: Vasconcellos
authors.forename: Ana L T O
authors.initials: AL
authors.lastname: Nascimento
mesh_terms: D000614:Aminocaproates / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002457:Cell Extracts; D003179:Complement C3b / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation; D005341:Fibrinolysin / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D007919:Leptospira / Q000166:cytology* / Q000378:metabolism*; D007922:Leptospirosis / Q000097:blood / Q000276:immunology / Q000382:microbiology; D050296:Microbial Viability; D008856:Microscopy, Fluorescence; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D040901:Proteomics; D011994:Recombinant Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D000614:Aminocaproates; D001426:Bacterial Proteins; D002457:Cell Extracts; D005353:Fibronectins; D055767:Immobilized Proteins; D007106:Immune Sera; D007074:Immunoglobulin G; D007797:Laminin; D011994:Recombinant Proteins; D003179:Complement C3b; D010958:Plasminogen; D005341:Fibrinolysin