新生隐球菌的病原学特性及耐药机制研究进展

Research progress in pathological properties and antifungal resistance mechanisms of Cryptococcus neoformans

摘要:

新生隐球菌(Cryptococcus neoformans)是一种常见机会致病菌，因其嗜中枢性，常引发隐球菌性脑膜炎。新生隐球菌的侵袭能力与多种因素密切相关，包括荚膜多糖、黑色素、水解酶等毒力因子，以及对宿主体内环境的适应性。在诊断方面，尽管传统方法如真菌培养和印度墨汁染色仍在使用，但其局限性显而易见。相较之下，分子检测、影像技术和生物芯片等新兴手段显著提升了隐球菌感染的诊断准确性和灵敏度。在临床治疗方面，两性霉素B和氟康唑作为一线药物被广泛应用，但唑类药物的耐药问题日益严峻，导致临床治疗失败率升高。这种耐药性主要归因于靶点基因突变、外排泵表达上调及基因组倍性改变。针对其毒力因子和耐药机制的深入研究，促进了新型抗真菌疗法的探索，包括旧药新用、新药研发以及创新给药策略。本文结合最新研究，综述了新生隐球菌的毒力因子、诊断技术进展、耐药机制及新疗法的研究动态，旨在为隐球菌病的临床诊疗提供借鉴与启示。

关键词:新生隐球菌;毒力因子;诊断方法;耐药机制

Abstract:

Cryptococcus neoformans is a common opportunistic pathogen, exhibiting pronounced neurotropism that often results in cryptococcal meningitis. Its invasive ability is closely associated with multiple factors, including capsular polysaccharides, melanin, hydrolases, and adaptability to the host environment. Conventional diagnostic methods such as fungal culture and India ink staining, though still in use, have notable limitations, whereas emerging techniques like molecular diagnostics, imaging technologies, and biochips have significantly enhanced the diagnostic accuracy and sensitivity. In clinical treatment, amphotericin B and fluconazole are widely used as first-line antifungals, while the resistance to azoles is a growing problem and results in an elevated rate of clinical treatment failure. This is mainly attributed to target alterations, upregulation of efflux pump expression and genomic ploidy changes. Recent studies on virulence factors and resistance mechanisms have driven the development of novel antifungal therapies, including drug repurposing, novel drug development, and innovative drug delivery strategies. This article reviews the latest research in the virulence factors, diagnostic techniques, antifungal resistance mechanisms, and therapeutic development of C. neoformans, providing insights into the clinical management of cryptococcosis.

Key words:Cryptococcus neoformans;virulence factors;diagnostic methods;resistance mechanisms