Candidiasis is a fungal infection caused by Candida spp. especially Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis. Although the medicinal therapeutic strategies have rapidly improved, the mortality rate as candidiasis has continuously increased. The secreted and membrane-bound virulence factors (VFs) are responsible for fungal invasion, damage and translocation through the host enterocytes besides the evasion from host immune system. VFs such as agglutinin-like sequences (Als), heat shock protein 70, phospholipases, secreted aspartyl proteinases (Sap), lipases, enolases and phytases are mostly hydrolases which degrade or interact with the enterocyte membrane components. Candidalysin, however, acts as a peptide toxin to induce necrotic cell lysis. To date, structural studies of the VFs remain underexplored, hindering their functional analyses. Among the VFs, only Sap and Als have their structures deposited in Protein Data Bank (PDB). Therefore, this review scrutinizes the mechanisms of these VFs by discussing the VF-deficient studies of several Candida spp. and their abilities to produce these VFs. Nonetheless, their latest reported sequential and structural analyses are discussed to impart a wider perception of the host-pathogen interactions and potential vaccine or antifungal drug targets. This review signifies that more VFs structural investigations and mining in the emerging Candida spp. are required to decipher their pathogenicity and virulence mechanisms compared to the prominent C. albicans. Lay summary Candida virulence factors (VFs) including mainly enzymes and proteins play vital roles in breaching the human intestinal barrier and causing deadly invasive candidiasis. Limited VFs’ structural studies hinder deeper comprehension of their mechanisms and thus the design of vaccines and antifungal drugs against fungal infections.

中文翻译：

---

机会性酵母病原体念珠菌属：分泌的和膜结合的毒力因子

念珠菌病是由念珠菌属引起的真菌感染。特别是白色念珠菌、光滑念珠菌、近平滑念珠菌和热带念珠菌。尽管药物治疗策略已迅速改善，但念珠菌病的死亡率却不断增加。除了逃避宿主免疫系统外，分泌的和膜结合的毒力因子 (VFs) 还负责真菌通过宿主肠细胞的侵袭、损伤和易位。诸如凝集素样序列 (Als)、热休克蛋白 70、磷脂酶、分泌天冬氨酰蛋白酶 (Sap)、脂肪酶、烯醇化酶和植酸酶等 VF 大多是水解酶，它们降解或与肠细胞膜成分相互作用。然而，念珠菌溶素作为肽毒素诱导坏死细胞裂解。迄今为止，对 VF 的结构研究仍未得到充分探索，阻碍他们的功能分析。在 VF 中，只有 Sap 和 Als 的结构保存在蛋白质数据库 (PDB) 中。因此，本综述通过讨论几种念珠菌属的 VF 缺陷研究来仔细检查这些 VFs 的机制。以及他们制作这些 VF 的能力。尽管如此，讨论了他们最新报道的顺序和结构分析，以更广泛地了解宿主-病原体相互作用和潜在的疫苗或抗真菌药物靶点。该审查表明在新兴的念珠菌属中进行了更多的 VFs 结构调查和挖掘。与突出的白色念珠菌相比，需要破译其致病性和毒力机制。总结 念珠菌毒力因子 (VFs) 主要包括酶和蛋白质，在破坏人体肠道屏障和导致致命的侵袭性念珠菌病方面发挥着至关重要的作用。有限的 VF 结构研究阻碍了对其机制的更深入理解，从而阻碍了针对真菌感染的疫苗和抗真菌药物的设计。