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Sporothrix schenckii Peptidorhamnomannan-Associated Protein 2 (Pap2) Is Involved in Adhesion and Virulence
Dario A Baruch-Martínez1, Manuela Gómez-Gaviria1, Joaquín O Chávez-Santiago1
1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato, Gto, Mexico.
Introduction:
The Sporothrix schenckii cell wall has been widely studied to understand its role in pathogenesis and the infection process. Previously, a component of the cell wall, the peptidorhamnomannan (PRM), was analyzed, and some proteins with unknown function were identified. Among them, the protein encoded by the SPSK_06559 gene stood out for its high abundance within PRM.
Methods:
In this work, in silico analyses were performed to predict the adhesive properties of the SPSK_06559 protein (renamed as Pap2) to extracellular matrix (ECM) components, such as fibrinogen, fibronectin, and type-I and type-II collagen. Subsequently, a recombinant Pap2 (rPap2) version was generated to obtain experimental evidence of its adhesive properties to ECM components. Finally, the role of Pap2 in pathogenesis was assessed in Galleria mellonella larvae.
Results:
Bioinformatic analyses consistently suggested that Pap2 possesses adhesive properties. Prediction was experimental validated: rPap2 showed strong adhesion to ECM components. Immunization with rPap2 conferred significant protection to G. mellonella larvae against a lethal dose of S. schenckii. Furthermore, preincubation of fungal cells with anti-rPap2 antibodies drastically reduced their ability to kill the larvae.
Discussion:
These findings demonstrate that the SPSK_06559 protein (Pap2) participates in the initial adhesion to host tissues. Induction of a protective response through immune priming with rPap2 suggest that Pap2 is a promising immunogenic antigen. Reduction of lethality upon blocking Pap2 confirms its essential role in pathogenesis, positioning it as a potential target for the development of new therapies and vaccines against sporotrichosis.
Insights
The newly identified Pap2 protein in Sporothrix schenckii aids fungal adhesion to host tissues. Immunization with Pap2 offers protection against sporotrichosis, highlighting its potential as a therapeutic target.
Area of Science:
- Mycology
- Pathogenesis
- Immunology
Background:
- The cell wall of *Sporothrix schenckii* is crucial for pathogenesis.
- Previous studies identified proteins of unknown function within the peptidorhamnomannan (PRM) cell wall component.
- The protein encoded by the SPSK_06559 gene was highly abundant in PRM.
Purpose of the Study:
- To investigate the adhesive properties of the SPSK_06559 protein (Pap2) to extracellular matrix (ECM) components.
- To experimentally validate the predicted adhesive properties of Pap2.
- To assess the role of Pap2 in *Sporothrix schenckii* pathogenesis using a *Galleria mellonella* infection model.
Main Methods:
- In silico analysis to predict Pap2 adhesion to ECM components (fibrinogen, fibronectin, collagens).
- Generation of recombinant Pap2 (rPap2) for experimental validation.
- Assessment of Pap2's role in pathogenesis in *Galleria mellonella* larvae.
Main Results:
- Bioinformatic predictions indicated Pap2 possesses adhesive properties.
- Experimental validation confirmed strong adhesion of rPap2 to ECM components.
- Immunization with rPap2 provided significant protection to *G. mellonella* larvae against *S. schenckii*.
- Blocking Pap2 with antibodies reduced fungal lethality in larvae.
Conclusions:
- Pap2 facilitates initial adhesion to host tissues during *Sporothrix schenckii* infection.
- Pap2 is a promising immunogenic antigen for vaccine development against sporotrichosis.
- Pap2 plays an essential role in pathogenesis and is a potential therapeutic target.
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