Joshi Pooja, Navale Archana, Shelke Ajay, Patel Muskan
Department of Pharmacology, Parul Institute of Pharmacy, Parul University, Limda, Waghodia, Vadodara, Gujarat, India.
Curr Pharm Biotechnol. 2024 Sep 13. doi: 10.2174/0113892010304880240828075411.
Fungal infections contribute to over 1.5 million fatalities each year, with cutaneous mycoses standing as prominent global infections. The spectrum of these mycoses varies widely, encompassing enduring afflictions like ringworm, localized infections such as tinea capitis, recurrent instances like vaginal candidiasis, and potentially fatal systemic infections impacting multiple organ systems. The escalating recognition of the health and socioeconomic ramifications associated with fungal pathogens underscores their importance in contemporary discourse. On a global scale, projections indicate that over 300 million individuals experience significant fungal infections annually, resulting in a mortality rate exceeding 1.5 million deaths per year. Alarmingly, resistance to commonly used antifungal drugs was on the rise, with some reports suggesting that over 10% of Candida bloodstream isolates worldwide were resistant to fluconazole, a commonly prescribed antifungal medication. Therefore, there is an immediate need to increase the accessibility of new antifungal medications while minimizing their costs and adverse effects. Fungi, as heterotrophic organisms, acquire nutrients through absorption. Their filamentous structure, composed of hyphae, facilitates efficient nutrient uptake by secreting enzymes that break down complex organic matter into simpler compounds. These organisms exhibit remarkable adaptability in responding to environmental cues, adjusting growth rates, and altering morphological features. Fungi regulate their metabolism intricately, undergoing various metabolic pathways for energy production and utilizing diverse substrates for respiration. Additionally, they exhibit distinctive reproductive strategies, employing both sexual and asexual modes of reproduction, contributing to their genetic diversity and resilience in diverse ecosystems. We now have more information than ever on the origins of infection as well as the physiology of fungi cells, giving us the chance to use it to produce new generations of antifungals. This review includes various novel antifungal drug targets showing their possible effects via different mechanisms aiming at vital functions like GPI synthesis, cell wall synthesis, hyphal growth, and other essential pathways responsible for fungal growth.
真菌感染每年导致超过150万人死亡，皮肤真菌病是全球范围内的主要感染病。这些真菌病的范围广泛，包括像癣这样的持续性疾病、如头癣的局部感染、像阴道念珠菌病这样的复发性病例，以及影响多个器官系统的潜在致命性全身感染。对与真菌病原体相关的健康和社会经济影响的认识不断提高，凸显了它们在当代讨论中的重要性。在全球范围内，预测表明每年有超过3亿人遭受严重的真菌感染，导致每年死亡率超过150万例。令人担忧的是，对常用抗真菌药物的耐药性正在上升，一些报告表明全球超过10%的念珠菌血流分离株对氟康唑耐药，氟康唑是一种常用的抗真菌药物。因此，迫切需要增加新抗真菌药物的可及性，同时尽量降低其成本和副作用。真菌作为异养生物，通过吸收获取营养。它们由菌丝组成的丝状结构通过分泌将复杂有机物分解为更简单化合物的酶来促进有效的营养吸收。这些生物在响应环境线索、调节生长速率和改变形态特征方面表现出显著的适应性。真菌复杂地调节其新陈代谢，经历各种代谢途径进行能量产生，并利用多种底物进行呼吸。此外，它们表现出独特的繁殖策略，采用有性和无性繁殖方式，这有助于它们在不同生态系统中的遗传多样性和恢复力。我们现在比以往任何时候都更了解感染的起源以及真菌细胞的生理学，这使我们有机会利用这些信息生产新一代的抗真菌药物。这篇综述包括各种新型抗真菌药物靶点，展示了它们通过不同机制针对如GPI合成、细胞壁合成、菌丝生长以及其他负责真菌生长的重要途径等关键功能可能产生的作用。
