Polypeptides Targeting Paracoccidioides brasiliensis Drk1

Author:

Marcos Caroline Maria1ORCID,de Oliveira Haroldo Cesar12ORCID,Assato Patricia Akemi13ORCID,de Oliveira Lariane Teodoro1,Fregonezi Nathália1,dos Santos Kelvin Sousa1ORCID,Costa-Orlandi Caroline Barcelos1ORCID,Fusco-Almeida Ana Marisa1,Mendes-Giannini Maria José Soares1ORCID

Affiliation:

1. School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil

2. Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba 81350-010, Brazil

3. Laboratório Central de Multiusuários, Faculdade de Ciências Agronômicas, Campus Botucatu, UNESP—Universidade Estadual Paulista, São Paulo 18610-034, Brazil

Abstract

Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the numerous factors underpinning the establishment of Paracoccidioides spp. infection, the capacity to transition from the mycelial to the yeast form is of pivotal importance. The Drk1 protein of Paracoccidioides brasiliensis likely plays a decisive role in this morphological shift and subsequent virulence. We identified peptides with affinity for the PbDrk1 protein using the phage-display method and assessed the effects of these peptides on P. brasiliensis. The peptides were found to inhibit the phase transition of P. brasiliensis. Furthermore, a substantial proportion of these peptides prevented adhesion to pneumocytes. Although these peptides may not possess inherent antifungal properties, they can augment the effects of certain antifungal agents. Notably, the cell wall architecture of P. brasiliensis appears to be modulated by peptide intervention, resulting in a reduced abundance of glycosylated proteins and lipids. These peptides were also evaluated for their efficacy in a Galleria mellonella model and shown to contribute to enhanced larval survival rates. The role of PbDrk1, which is notably absent in mammals, should be further investigated to improve the understanding of its functional role in P. brasiliensis, which may be helpful for designing novel therapeutic modalities.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento Pessoal de Nível Superior

Programa de Apoio ao Desenvolvimento Científico da Faculdade de Ciências Farmacêuticas da UNESP

Publisher

MDPI AG

Subject

Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3