Cowen Leah E, Anderson James B, Kohn Linda M
Department of Botany, University of Toronto, Mississauga, Ontario, L5L 1C6, Canada.
Annu Rev Microbiol. 2002;56:139-65. doi: 10.1146/annurev.micro.56.012302.160907. Epub 2002 Jan 30.
The widespread deployment of antimicrobial agents in medicine and agriculture is nearly always followed by the evolution of resistance to these agents in the pathogen. With the limited availability of antifungal drugs and the increasing incidence of opportunistic fungal infections, the emergence of drug resistance in fungal pathogens poses a serious public health concern. Antifungal drug resistance has been studied most extensively with the yeast Candida albicans owing to its importance as an opportunistic pathogen and its experimental tractability relative to other medically important fungal pathogens. The emergence of antifungal drug resistance is an evolutionary process that proceeds on temporal, spatial, and genomic scales. This process can be observed through epidemiological studies of patients and through population-genetic studies of pathogen populations. Population-genetic studies rely on sampling of the pathogen in patient populations, serial isolations of the pathogen from individual patients, or experimental evolution of the pathogen in nutrient media or in animal models. Predicting the evolution of drug resistance is fundamental to prolonging the efficacy of existing drugs and to strategically developing and deploying novel drugs.
抗菌药物在医学和农业中的广泛应用几乎总会导致病原体对这些药物产生耐药性。由于抗真菌药物的供应有限以及机会性真菌感染的发病率不断上升,真菌病原体中耐药性的出现引起了严重的公共卫生问题。由于白色念珠菌作为一种机会性病原体的重要性及其相对于其他医学上重要的真菌病原体的实验易处理性,对其抗真菌药物耐药性的研究最为广泛。抗真菌药物耐药性的出现是一个在时间、空间和基因组尺度上进行的进化过程。这个过程可以通过对患者的流行病学研究以及对病原体群体的群体遗传学研究来观察。群体遗传学研究依赖于在患者群体中对病原体进行采样、从个体患者中连续分离病原体,或者在营养培养基或动物模型中对病原体进行实验进化。预测耐药性的演变对于延长现有药物的疗效以及从战略上开发和部署新型药物至关重要。