PDF(Pubmed)
Abstract：
Cryptococcus spp., in particular Cryptococcus neoformans and Cryptococcus gattii, have an enormous impact on human health worldwide. The global burden of cryptococcal meningitis is almost a quarter of a million cases and 181,000 deaths annually, with mortality rates of 100% if infections remain untreated. Despite these alarming statistics, treatment options for cryptococcosis remain limited, with only three major classes of drugs approved for clinical use. Exacerbating the public health burden is the fact that the only new class of antifungal drugs developed in decades, the echinocandins, displays negligible antifungal activity against Cryptococcus spp., and the efficacy of the remaining therapeutics is hampered by host toxicity and pathogen resistance. Here, we describe the current arsenal of antifungal agents and the treatment strategies employed to manage cryptococcal disease. We further elaborate on the recent advances in our understanding of the intrinsic and adaptive resistance mechanisms that are utilized by Cryptococcus spp. to evade therapeutic treatments. Finally, we review potential therapeutic strategies, including combination therapy, the targeting of virulence traits, impairing stress response pathways and modulating host immunity, to effectively treat infections caused by Cryptococcus spp. Overall, understanding of the mechanisms that regulate anti-cryptococcal drug resistance, coupled with advances in genomics technologies and high-throughput screening methodologies, will catalyse innovation and accelerate antifungal drug discovery.
摘要：
隐球菌属。,特别是新生隐球菌和加蒂隐球菌，对全球人类健康产生巨大影响。隐球菌性脑膜炎的全球负担是每年近25万例病例和181,000例死亡，如果不治疗感染，死亡率为100%。尽管有这些令人震惊的统计数字,隐球菌病的治疗选择仍然有限，只有三类药物被批准用于临床。加剧公共卫生负担的事实是，几十年来开发的唯一一类新的抗真菌药物，棘白菌素,对隐球菌的抗真菌活性可忽略不计。,其余治疗剂的功效受到宿主毒性和病原体抗性的阻碍。这里,我们描述了目前的抗真菌药物库以及用于治疗隐球菌病的治疗策略.我们进一步阐述了我们对隐球菌属利用的内在和适应性抗性机制的理解的最新进展。逃避治疗。最后,我们回顾了潜在的治疗策略，包括联合治疗,毒力性状的靶向，损害应激反应途径和调节宿主免疫，有效治疗由隐球菌引起的感染。总的来说,了解调节抗隐球菌耐药性的机制，加上基因组学技术和高通量筛选方法的进步，将促进创新并加速抗真菌药物的发现。
