Vandeputte Patrick, Ferrari Selene, Coste Alix T
Institute of Microbiology, University of Lausanne and University Hospital, Rue du Bugnon 48, 1011 Lausanne, Switzerland.
Int J Microbiol. 2012;2012:713687. doi: 10.1155/2012/713687. Epub 2011 Dec 1.
Despite improvement of antifungal therapies over the last 30 years, the phenomenon of antifungal resistance is still of major concern in clinical practice. In the last 10 years the molecular mechanisms underlying this phenomenon were extensively unraveled. In this paper, after a brief overview of currently available antifungals, molecular mechanisms of antifungal resistance will be detailed. It appears that major mechanisms of resistance are essential due to the deregulation of antifungal resistance effector genes. This deregulation is a consequence of point mutations occurring in transcriptional regulators of these effector genes. Resistance can also follow the emergence of point mutations directly in the genes coding antifungal targets. In addition we further describe new strategies currently undertaken to discover alternative therapy targets and antifungals. Identification of new antifungals is essentially achieved by the screening of natural or synthetic chemical compound collections. Discovery of new putative antifungal targets is performed through genome-wide approaches for a better understanding of the human pathogenic fungi biology.
尽管在过去30年里抗真菌治疗有所改进，但抗真菌耐药现象在临床实践中仍是主要关注点。在过去10年里，这一现象背后的分子机制被广泛揭示。本文在简要概述目前可用的抗真菌药物后，将详细阐述抗真菌耐药的分子机制。似乎主要的耐药机制是由于抗真菌耐药效应基因的失调所致。这种失调是这些效应基因转录调节因子中发生点突变的结果。耐药性也可能直接源于编码抗真菌靶点的基因中出现点突变。此外，我们还进一步描述了目前为发现替代治疗靶点和抗真菌药物而采取的新策略。新抗真菌药物的鉴定主要通过筛选天然或合成化合物库来实现。通过全基因组方法来发现新的潜在抗真菌靶点，以便更好地了解人类致病真菌生物学。
