Paracoccin Overexpression in Paracoccidioides brasiliensis Enhances Fungal Virulence by Remodeling Chitin Properties of the Cell Wall

Author(s)

Goncales, Relber Aguiar ^{[1, 2, 3]} ; Ricci-Azevedo, Rafael ^[2] ; Vieira, Vanessa C. S. ^[3] ; Fernandes, Fabricio F. ^[2] ; Thomaz, Sandra M. de O. ^[2] ; Carvalho, Agostinho ^{[1, 3]} ; Vendruscolo, Patricia E. ^[2] ; Cunha, Cristina ^{[1, 3]} ; Roque-Barreira, Maria Cristina ^[2] ; Rodrigues, Fernando ^{[1, 3]}

Affiliation

^[1] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto - Brazil

^[3] Univ Minho, Life & Hlth Sci Res Inst, Sch Med, Braga - Portugal

• Document type: Journal article
• Source: Journal of Infectious Diseases; v. 224, n. 1, p. 164-174, JUL 1 2021.
• Web of Science Citations: 0

Abstract

Background: The thermodimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis. Although poorly studied, paracoccin (PCN) from Paracoccidioides brasiliensis has been shown to harbor lectinic, enzymatic, and immunomodulatory properties that affect disease development. Methods: Mutants of P. brasiliensis overexpressing PCN (ov-PCN) were constructed by Agrobacterium tumefaciens-mediated transformation. ov-PCN strains were analyzed and inoculated intranasally or intravenously to mice. Fungal burden, lung pathology, and survival were monitored to evaluate virulence. Electron microscopy was used to evaluate the size of chito-oligomer particles released by ov-PCN or wild-type strains to growth media. Results: ov-PCN strains revealed no differences in cell growth and viability, although PCN overexpression favored cell separation, chitin processing that results in the release of smaller chito-oligomer particles, and enhanced virulence. Our data show that PCN triggers a critical effect in the cell wall biogenesis through the chitinase activity resulting from overexpression of PCN. As such, PCN overexpression aggravates the disease caused by P. brasiliensis. Conclusions: Our data are consistent with a model in which PCN modulates the cell wall architecture via its chitinase activity. These findings highlight the potential for exploiting PCN function in future therapeutic approaches. (AU)

• FAPESP's process: 14/22561-7 - Overexpression of paracoccin: phenotype and virulence of Paracoccidioides brasiliensis strains
• Grantee: Relber Aguiar Gonçales
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/02998-0 - Effects of Toxoplasma gondii and Paracoccidioides brasiliensis, exerted through their respective lectins on intracellular pathways activated by the recognition of N-linked glycans to toll like receptors on neutrophils
• Grantee: Rafael Ricci de Azevedo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/04088-0 - Lectin from pathogens
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/21708-5 - Application of immunomoduladors, by carbohydrate recognition, as therapeutic agents: mechanism of action to immunotherapy
• Grantee: Maria Cristina Roque Antunes Barreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/00629-4 - Characterization of enzymatic and lectin domains and the effects on innate immunity cell receptors
• Grantee: Fabrício Freitas Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral