Vale-Silva Luis A, Sanglard Dominique
Institute of Microbiology, University of Lausanne and University Hospital Center, CH-1011 Lausanne, Switzerland.
Institute of Microbiology, University of Lausanne and University Hospital Center, CH-1011 Lausanne, Switzerland
FEMS Yeast Res. 2015 Jun;15(4):fov025. doi: 10.1093/femsyr/fov025. Epub 2015 May 15.
Among existing fungal pathogens, Candida glabrata is outstanding in its capacity to rapidly develop resistance to currently used antifungal agents. Resistance to the class of azoles, which are still widely used agents, varies in proportion (from 5 to 20%) depending on geographical area. Moreover, resistance to the class of echinocandins, which was introduced in the late 1990s, is rising in several institutions. The recent emergence of isolates with acquired resistance to both classes of agents is a major concern since alternative therapeutic options are scarce. Although considered less pathogenic than C. albicans, C. glabrata has still evolved specific virulence traits enabling its survival and propagation in colonized and infected hosts. Development of drug resistance is usually associated with fitness costs, and this notion is documented across several microbial species. Interestingly, azole resistance in C. glabrata has revealed the opposite. Experimental models of infection showed enhanced virulence of azole-resistant isolates. Moreover, azole resistance could be associated with specific changes in adherence properties to epithelial cells or innate immunity cells (macrophages), both of which contribute to virulence changes. Here we will summarize the current knowledge on C. glabrata drug resistance and also discuss the consequences of drug resistance acquisition on the balance between C. glabrata and its hosts.
在现有的真菌病原体中，光滑念珠菌在快速产生对当前使用的抗真菌药物的耐药性方面表现突出。对仍被广泛使用的唑类药物的耐药性，因地理区域而异（从5%到20%不等）。此外，对20世纪90年代末引入的棘白菌素类药物的耐药性在一些机构中呈上升趋势。最近出现了对这两类药物均获得性耐药的分离株，这是一个主要问题，因为替代治疗选择很少。尽管光滑念珠菌被认为致病性低于白色念珠菌，但它仍进化出了特定的毒力特征，使其能够在定植和感染的宿主中存活和繁殖。耐药性的产生通常与适应性代价相关，这一概念在多种微生物中都有记载。有趣的是，光滑念珠菌中的唑类耐药性却呈现出相反的情况。感染实验模型显示，唑类耐药分离株具有更强的毒力。此外，唑类耐药可能与对上皮细胞或先天免疫细胞（巨噬细胞）的黏附特性的特定变化有关，这两者都导致了毒力的改变。在此，我们将总结目前关于光滑念珠菌耐药性的知识，并讨论获得耐药性对光滑念珠菌与其宿主之间平衡的影响。
