Staphylococcus aureus manganese transport protein C (MntC) is an extracellular matrix- and plasminogen-binding protein.

Natália Salazar,Íris Arantes De Castro,Hana Paula Masuda,Ludmila Bezerra Da Silva,Denize Monaris,Angela Silva Barbosa,Ana Paula Mattos Arêas,Mónica Marcela Castiblanco-Valencia,Catherine A Brissette

doi:10.1371/journal.pone.0112730

Natália Salazar, Íris Arantes De Castro + Show 7 more

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https://doi.org/10.1371/journal.pone.0112730

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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.

Highlights

Staphylococcus aureus is the causative agent of potentially harmful diseases, like necrotizing pneumonia, sepsis and endocarditis, and it is responsible for less severe clinical manifestations such as epithelial and mucosal-associated infections
Considering that during infection important virulence factors of many pathogens may interact with multiple host proteins, including extracellular matrix (ECM) and coagulation cascade molecules, we evaluated whether Manganese transport protein C (MntC) would contribute to staphylococcal colonization and dissemination by interacting with multiple ECM molecules as well as with plasminogen
Expression and purification of MntC Recombinant MntC was expressed in E. coli BL21 (DE3) in the soluble fraction

Summary

Introduction

Staphylococcus aureus is the causative agent of potentially harmful diseases, like necrotizing pneumonia, sepsis and endocarditis, and it is responsible for less severe clinical manifestations such as epithelial and mucosal-associated infections. In spite of the advances in antibiotic development, treating these infections remains a huge challenge. Since this bacterium was isolated from a patient [2] and its effects in the host were described [3], great efforts have been made to understand and characterize virulence factors involved in the pathogenesis. A major class of proteins, responsible for the survival of the microorganism in the host, is surface proteins They are protagonists in acquisition of cellular nutrients and in adherence to mucosal cells or the extracellular matrix (ECM), in the earlier stages of pathogenesis. They are implicated in the invasion of sterile sites through the disruption of ECM integrity at mucosal and epithelial tissues (reviewed in [6])

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