Hameed Saif, Hans Sandeep, Singh Shweta, Fatima Zeeshan
Amity Institute of Biotechnology, Amity University Haryana, Gurugram (Manesar)-122413, India.
Curr Drug Discov Technol. 2020;17(4):415-429. doi: 10.2174/1570163816666190227231437.
Fungal infections, particularly of Candida species, which are the commensal organisms of human, are one of the major debilitating diseases in immunocompromised patients. The limited number of antifungal drugs available to treat Candida infections, with the concomitant increasing incidence of multidrug-resistant (MDR) strains, further worsens the therapeutic options. Thus, there is an urgent need for the better understanding of MDR mechanisms, and their reversal, by employing new strategies to increase the efficacy and safety profiles of currently used therapies against the most prevalent human fungal pathogen, Candida albicans. Micronutrient availability during C. albicans infection is regarded as a critical factor that influences the progression and magnitude of the disease. Intracellular pathogens colonize a variety of anatomical locations that are likely to be scarce in micronutrients, as a defense strategy adopted by the host, known as nutritional immunity. Indispensable critical micronutrients are required both by the host and by C. albicans, especially as a cofactor in important metabolic functions. Since these micronutrients are not freely available, C. albicans need to exploit host reservoirs to adapt within the host for survival. The ability of pathogenic organisms, including C. albicans, to sense and adapt to limited micronutrients in the hostile environment is essential for survival and confers the basis of its success as a pathogen. This review describes that micronutrients availability to C. albicans is a key attribute that may be exploited when one considers designing strategies aimed at disrupting MDR in this pathogenic fungi. Here, we discuss recent advances that have been made in our understanding of fungal micronutrient acquisition and explore the probable pathways that may be utilized as targets.
真菌感染,尤其是念珠菌属感染,念珠菌属是人类的共生生物,是免疫功能低下患者的主要致残性疾病之一。可用于治疗念珠菌感染的抗真菌药物数量有限,同时多重耐药(MDR)菌株的发病率不断上升,这进一步恶化了治疗选择。因此,迫切需要更好地了解多重耐药机制及其逆转方法,通过采用新策略来提高目前针对最常见的人类真菌病原体白色念珠菌的治疗方法的疗效和安全性。白色念珠菌感染期间的微量营养素可用性被认为是影响疾病进展和严重程度的关键因素。细胞内病原体定殖于各种可能缺乏微量营养素的解剖位置,这是宿主采取的一种防御策略,称为营养免疫。宿主和白色念珠菌都需要不可或缺的关键微量营养素,尤其是作为重要代谢功能的辅助因子。由于这些微量营养素并非随时可用,白色念珠菌需要利用宿主储备在宿主体内适应生存。包括白色念珠菌在内的致病生物感知并适应恶劣环境中有限微量营养素的能力对于生存至关重要,并为其作为病原体成功的基础。这篇综述描述了白色念珠菌的微量营养素可用性是一个关键属性,在考虑设计旨在破坏这种致病真菌多重耐药性的策略时可能会被利用。在这里,我们讨论了我们在理解真菌微量营养素获取方面取得的最新进展,并探索了可能用作靶点的潜在途径。