Sporothrix schenckii Peptidorhamnomannan-Associated Protein 2 (Pap2) Is Involved in Adhesion and Virulence

Dario A Baruch-Martínez,1 Manuela Gómez-Gaviria,1 Joaquín O Chávez-Santiago,1 Uriel Ramírez-Sotelo,1 Luisa M Contreras-López,1 Iván Martínez-Duncker,2 Andréa Regina Souza Baptista,3 Héctor M Mora-Montes1 1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Guanajuato, Gto, Mexico; 2Laboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mor, Mexico; 3Centro de Investigação de Microrganismos, Instituto Biomédico, Universidade Federal Fluminense, Niterói, RJ, BrazilCorrespondence: Héctor M Mora-Montes, Email [email protected]: 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.Keywords: cell wall, glycoproteins, immune priming, peptidorhamnomannan, recombinant protein