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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF FUNGI; v. 7, n. 10 OCT 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 16/17048-4 - Sistema de dois componentes de transdução de sinais (TCST) como novo alvo para o delineamento de peptídeos antifúngicos
• Beneficiário: Caroline Maria Marcos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/14023-8 - Uso de peptídeos com atividade anti-adesiva em Paracoccidoides spp. na terapêutica e profilaxia da paracoccidioidomicose
• Beneficiário: Haroldo Cesar de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/03700-9 - Animais alternativos aplicados à interação Paracoccidioides-hospedeiro para o desenvolvimento de estudos de virulência, eficácia e toxicidade de compostos antifúngicos e tratamentos preventivos
• Beneficiário: Maria José Soares Mendes Giannini
• Modalidade de apoio: Auxílio à Pesquisa - Regular