Almeida Fausto, Antoniêto Amanda Cristina Campos, Pessoni André Moreira, Monteiro Valdirene Neves, Alegre-Maller Ana Claudia Paiva, Pigosso Laurine Lacerda, Pereira Maristela, Soares Célia Maria de Almeida, Roque-Barreira Maria Cristina
Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14049-900, Brazil;
Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP 14040-900, Brazil;
Curr Genomics. 2016 Apr;17(2):112-8. doi: 10.2174/1389202917666151116212705.
Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America. It is caused by the temperature-dependent dimorphic fungus Paracoccidioides brasiliensis. The P. brasiliensis cell wall is a dynamic outer structure, composed of a network of glycoproteins and polysaccharides, such as chitin, glucan and N-glycosylated proteins. These glycoproteins can interact with the host to affect infection rates, and are known to perform other functions. We inhibited N-linked glycosylation using tunicamycin (TM), and then evaluated the expression of P. brasiliensis genes related to cell wall remodeling. Our results suggest that cell wall synthesis related genes, such as β-1,3-glucanosyltransferase (PbGEL3), 1,3-β-D-glucan synthase (PbFKS1), and α-1,4-amylase (PbAMY), as well as cell wall degrading related genes, such as N-acetyl-β-D-glucosaminidase (PbNAG1), α-1,3-glucanase (PbAGN), and β-1,3-glucanase (PbBGN1 and PbBGN2), have their expression increased by the N-glycosylation inhibition, as detected by qRT-PCR. The observed increases in gene expression levels reveal possible compensatory mechanisms for diminished enzyme activity due to the lack of glycosylation caused by TM.
副球孢子菌病是拉丁美洲最常见的系统性真菌病。它由温度依赖性双态真菌巴西副球孢子菌引起。巴西副球孢子菌的细胞壁是一个动态的外部结构,由糖蛋白和多糖网络组成,如几丁质、葡聚糖和N-糖基化蛋白。这些糖蛋白可与宿主相互作用以影响感染率,并且已知具有其他功能。我们使用衣霉素(TM)抑制N-糖基化,然后评估巴西副球孢子菌中与细胞壁重塑相关基因的表达。我们的结果表明,细胞壁合成相关基因,如β-1,3-葡聚糖基转移酶(PbGEL3)、1,3-β-D-葡聚糖合酶(PbFKS1)和α-1,4-淀粉酶(PbAMY),以及细胞壁降解相关基因,如N-乙酰-β-D-葡糖胺酶(PbNAG1)、α-1,3-葡聚糖酶(PbAGN)和β-1,3-葡聚糖酶(PbBGN1和PbBGN2),通过qRT-PCR检测发现其表达因N-糖基化抑制而增加。观察到的基因表达水平增加揭示了由于TM导致的糖基化缺乏而使酶活性降低的可能补偿机制。