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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Drk1, a Dimorphism Histidine Kinase, Contributes to Morphology, Virulence, and Stress Adaptation in Paracoccidioides brasiliensis

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Author(s):
Marcos, Caroline Maria [1] ; de Oliveira, Haroldo Cesar [1, 2] ; Assato, Patricia Akemi [1, 3] ; Castelli, Rafael Fernando [2, 4] ; Fusco-Almeida, Ana Marisa [1] ; Mendes-Giannini, Maria Jose Soares [1]
Total Authors: 6
Affiliation:
[1] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, BR-14800903 Araraquara, SP - Brazil
[2] Fundacao Oswaldo Cruz Fiocruz, Inst Carlos Chagas, BR-81350010 Curitiba, Parana - Brazil
[3] UNESP Univ Estadual Paulista, Fac Ciencias Agron, Lab Cent Multiusuarios, Campus Botucatu, BR-18610034 Sao Paulo - Brazil
[4] Fundacao Oswaldo Cruz Fiocruz, Inst Oswaldo Cruz, Programa Posgrad Biol Parasitaria, BR-21040360 Rio De Janeiro - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF FUNGI; v. 7, n. 10 OCT 2021.
Web of Science Citations: 0
Abstract

P. brasiliensis is a thermally dimorphic fungus belonging to Paracoccidioides complex, causative of a systemic, endemic mycosis limited to Latin American countries. Signal transduction pathways related to important aspects as surviving, proliferation according to the biological niches are linked to the fungal pathogenicity in many species, but its elucidation in P. brasiliensis remains poorly explored. As Drk1, a hybrid histidine kinase, plays regulators functions in other dimorphic fungi species, mainly in dimorphism and virulence, here we investigated its importance in P. brasilensis. We, therefore generated the respective recombinant protein, anti-PbDrk1 polyclonal antibody and a silenced strain. The Drk1 protein shows a random distribution including cell wall location that change its pattern during osmotic stress condition; moreover the P. brasiliensis treatment with anti-PbDrk1 antibody, which does not modify the fungus's viability, resulted in decreased virulence in G. mellonella model and reduced interaction with pneumocytes. Down-regulating PbDRK1 yielded phenotypic alterations such as yeast cells with more elongated morphology, virulence attenuation in G. mellonella infection model, lower amount of chitin content, increased resistance to osmotic and cell wall stresses, and also caspofungin, and finally increased sensitivity to itraconazole. These observations highlight the importance of PbDrk1 to P. brasiliensis virulence, stress adaptation, morphology, and cell wall organization, and therefore it an interesting target that could help develop new antifungals.</p> (AU)

FAPESP's process: 16/17048-4 - Two-component signal transduction (TCST) system as a new target for the treatment of paracoccidioidomycosis
Grantee:Caroline Maria Marcos
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
Grantee:Haroldo Cesar de Oliveira
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
Grantee:Maria José Soares Mendes Giannini
Support Opportunities: Regular Research Grants