title: The multifaceted roles of Leptospira enolase.
abstract: A previous study had demonstrated that Leptospira enolase is secreted extracellularly by a yet unknown mechanism and reassociates with the bacterial membrane. Surface-anchored leptospiral enolase displays plasminogen binding activity. In this work, we explored the consequences of this interaction and also assessed whether Leptospira enolase might display additional moonlighting functions by interacting with other host effector proteins. We first demonstrated that enolase-bound plasminogen is converted to its active form, plasmin. The protease plasmin targets human fibrinogen and vitronectin, but not the complement proteins C3b and C5. Leptospira enolase also acts as an immune evasion protein by interacting with the negative complement regulators C4b binding protein and factor H. Once bound to enolase, both regulators remain functional as cofactors of factor I, mediating cleavage of C4b and C3b. In conclusion, enolase may facilitate leptospiral survival and dissemination, thus contributing to bacterial virulence. The identification and characterization of moonlighting proteins is a growing field of bacterial pathogenesis, as these multifaceted proteins may represent potential future therapeutic targets to fight bacterial infections.
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. Electronic address: natsalazar@gmail.com.
authors.forename: Natália
authors.initials: N
authors.lastname: Salazar
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. Electronic address: matilde.souza@butantan.gov.br.
authors.forename: Matilde Costa Lima de
authors.initials: MC
authors.lastname: Souza
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. Electronic address: amandabiasioli@msn.com.
authors.forename: Amanda Gameiro
authors.initials: AG
authors.lastname: Biasioli
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. Electronic address: ludmila.silva@butantan.gov.br.
authors.forename: Ludmila Bezerra da
authors.initials: LB
authors.lastname: Silva
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, Av. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil. Electronic address: angela.barbosa@butantan.gov.br.
authors.forename: Angela Silva
authors.initials: AS
authors.lastname: Barbosa
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003179:Complement C3b / Q000737:chemistry / Q000378:metabolism; D050716:Complement C4b-Binding Protein; D003182:Complement C5 / Q000737:chemistry / Q000378:metabolism; D017242:Complement Factor H / Q000737:chemistry / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007919:Leptospira / Q000201:enzymology* / Q000472:pathogenicity; D010751:Phosphopyruvate Hydratase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding
chemical_list: D001426:Bacterial Proteins; D050716:Complement C4b-Binding Protein; D003182:Complement C5; D003179:Complement C3b; D017242:Complement Factor H; D010958:Plasminogen; D005341:Fibrinolysin; D010751:Phosphopyruvate Hydratase
keywords: C4b binding protein; Enolase; Factor H; Leptospira; Plasminogen