title: Staphylococcus aureus manganese transport protein C (MntC) is an extracellular matrix- and plasminogen-binding protein.
abstract: Infections caused by Staphylococcus aureus--particularly nosocomial infections--represent a great concern. Usually, the early stage of pathogenesis consists on asymptomatic nasopharynx colonization, which could result in dissemination to other mucosal niches or invasion of sterile sites, such as blood. This pathogenic route depends on scavenging of nutrients as well as binding to and disrupting extracellular matrix (ECM). Manganese transport protein C (MntC), a conserved manganese-binding protein, takes part in this infectious scenario as an ion-scavenging factor and surprisingly as an ECM and coagulation cascade binding protein, as revealed in this work. This study showed a marked ability of MntC to bind to several ECM and coagulation cascade components, including laminin, collagen type IV, cellular and plasma fibronectin, plasminogen and fibrinogen by ELISA. The MntC binding to plasminogen appears to be related to the presence of surface-exposed lysines, since previous incubation with an analogue of lysine residue, ε-aminocaproic acid, or increasing ionic strength affected the interaction between MntC and plasminogen. MntC-bound plasminogen was converted to active plasmin in the presence of urokinase plasminogen activator (uPA). The newly released plasmin, in turn, acted in the cleavage of the α and β chains of fibrinogen. In conclusion, we describe a novel function for MntC that may help staphylococcal mucosal colonization and establishment of invasive disease, through the interaction with ECM and coagulation cascade host proteins. These data suggest that this potential virulence factor could be an adequate candidate to compose an anti-staphylococcal human vaccine formulation.
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABCSanto André, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Salazar
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Mónica Marcela
authors.initials: MM
authors.lastname: Castiblanco-Valencia
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ludmila Bezerra
authors.initials: LB
authors.lastname: da Silva
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Íris  Arantes
authors.initials: Í
authors.lastname: de Castro
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Denize
authors.initials: D
authors.lastname: Monaris
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABCSanto André, Brazil.
authors.forename: Hana Paula
authors.initials: HP
authors.lastname: Masuda
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Angela Silva
authors.initials: AS
authors.lastname: Barbosa
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABCSanto André, Brazil.
authors.forename: Ana Paula Mattos
authors.initials: AP
authors.lastname: Arêas
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001777:Blood Coagulation; D017124:Conserved Sequence; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D008239:Lysine; D051379:Mice; D009994:Osmolar Concentration; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D013211:Staphylococcus aureus / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D005340:Fibrinogen; D010958:Plasminogen; D005341:Fibrinolysin; D008239:Lysine