de Oliveira Haroldo C, Michaloski Jussara S, da Silva Julhiany F, Scorzoni Liliana, de Paula E Silva Ana C A, Marcos Caroline M, Assato Patrícia A, Yamazaki Daniella S, Fusco-Almeida Ana M, Giordano Ricardo J, Mendes-Giannini Maria J S
Universidade Estadual Paulista (UNESP), Faculdade de Ciências Farmacêuticas, Câmpus Araraquara, São Paulo Brasil.
Universidade de São Paulo (USP), Instituto de Química, Câmpus São Paulo, São Paulo Brasil.
Front Pharmacol. 2016 Dec 23;7:509. doi: 10.3389/fphar.2016.00509. eCollection 2016.
and are dimorphic fungi and are the etiological agents of paracoccidioidomycosis (PCM). Adhesion is one of the most important steps in infections with s and is responsible for the differences in the virulence of isolates of these fungi. Because of the importance of adhesion to the establishment of an infection, this study focused on the preliminary development of a new therapeutic strategy to inhibit adhesion by , thus inhibiting infection and preventing the disease. We used two phage display libraries to select peptides that strongly bind to the cell wall to inhibit adhesion to host cells and extracellular matrix (ECM) components (laminin, fibronectin, and type I and type IV collagen). This approach allowed us to identify four peptides that inhibited up to 64% of the adhesion of to pneumocytes and inhibited the adhesion to the ECM components by up to 57%. Encouraged by these results, we evaluated the ability of these peptides to protect from infection by treating larvae with the different peptides prior to infection with and observing larval survival. The results show that all of the peptides tested increased the survival of the larvae infected with by up to 64% and by up to 60% in those infected with . These data may open new horizons for therapeutic strategies to prevent PCM, and anti-adhesion therapy could be an important strategy.
和是双相真菌，是副球孢子菌病（PCM）的病原体。黏附是感染和时最重要的步骤之一，也是这些真菌分离株毒力差异的原因。由于黏附对感染建立的重要性，本研究聚焦于初步开发一种新的治疗策略，即通过抑制的黏附来抑制感染并预防疾病。我们使用两个噬菌体展示文库来筛选与细胞壁强烈结合的肽，以抑制其对宿主细胞和细胞外基质（ECM）成分（层粘连蛋白、纤连蛋白以及I型和IV型胶原）的黏附。这种方法使我们鉴定出四种肽，它们可抑制高达64%的对肺细胞的黏附，并抑制对ECM成分的黏附达57%。受这些结果鼓舞，我们通过在感染之前用不同肽处理幼虫并观察幼虫存活情况，评估了这些肽保护免受感染的能力。结果表明，所有测试的肽都使感染的幼虫存活率提高了高达64%，使感染的幼虫存活率提高了高达60%。这些数据可能为预防PCM的治疗策略开辟新视野，抗黏附治疗可能是一种重要策略。
