Instituto de Investigaciones Biológicas, Universidad Nacional de Mar del Plata - Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Funes 3250, Mar del Plata 7600, Argentina.
Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.
Glycobiology. 2024 Jul 26;34(9). doi: 10.1093/glycob/cwae058.
The limited availability of efficient treatments for Candida infections and the increased emergence of antifungal-resistant strains stimulates the search for new antifungal agents. We have previously isolated a sunflower mannose-binding lectin (Helja) with antifungal activity against Candida albicans, capable of binding mannose-bearing oligosaccharides exposed on the cell surface. This work aimed to investigate the biological and biophysical basis of Helja's binding to C. albicans cell wall mannans and its influence on the fungicidal activity of the lectin. We evaluated the interaction of Helja with the cell wall mannans extracted from the isogenic parental strain (WT) and a glycosylation-defective C. albicans with altered cell wall phosphomannosylation (mnn4∆ null mutants) and investigated its antifungal effect. Helja exhibited stronger antifungal activity on the mutant strain, showing greater inhibition of fungal growth, loss of cell viability, morphological alteration, and formation of clusters with agglutinated cells. This differential biological activity of Helja was correlated with the biophysical parameters determined by solid phase assays and isothermal titration calorimetry, which demonstrated that the lectin established stronger interactions with the cell wall mannans of the mnn4∆ null mutant than with the WT strain. In conclusion, our results provide new evidence on the nature of the Helja molecular interactions with cell wall components, i.e. phosphomannan, and its impact on the antifungal activity. This study highlights the relevance of plant lectins in the design of effective antifungal therapies.
有限的有效治疗方法可用于治疗念珠菌感染，并且抗真菌耐药菌株的出现增加，这刺激了人们对新型抗真菌药物的研究。我们之前已经分离出一种向日葵甘露糖结合凝集素（Helja），它对白色念珠菌具有抗真菌活性，能够结合细胞表面暴露的带有甘露糖的寡糖。本研究旨在研究 Helja 与白色念珠菌细胞壁甘露聚糖结合的生物学和生物物理基础及其对凝集素杀菌活性的影响。我们评估了 Helja 与从同基因亲本菌株（WT）和糖基化缺陷的白色念珠菌（改变细胞壁磷酸甘露糖基化的 mnn4∆ 缺失突变体）中提取的细胞壁甘露聚糖的相互作用，并研究了其抗真菌作用。Helja 对突变株表现出更强的抗真菌活性，表现出更强的抑制真菌生长、丧失细胞活力、形态改变以及聚集形成带有凝集细胞的簇的能力。Helja 的这种差异生物学活性与固相测定和等温滴定量热法确定的生物物理参数相关，表明该凝集素与 mnn4∆ 缺失突变体的细胞壁甘露聚糖建立了更强的相互作用，而与 WT 菌株相比则较弱。总之，我们的结果提供了关于 Helja 与细胞壁成分（即磷酸甘露聚糖）的分子相互作用性质及其对抗真菌活性的影响的新证据。本研究强调了植物凝集素在设计有效抗真菌疗法中的相关性。
