Campbell Bruce C, Chan Kathleen L, Kim Jong H
Plant Mycotoxin Research Unit, Western Regional Research Center, Agricultural Research Service, United States Department of Agriculture Albany, CA, USA.
Front Microbiol. 2012 Feb 29;3:79. doi: 10.3389/fmicb.2012.00079. eCollection 2012.
Antimycotic chemosensitization and its mode of action are of growing interest. Currently, use of antifungal agents in agriculture and medicine has a number of obstacles. Foremost of these is development of resistance or cross-resistance to one or more antifungal agents. The generally high expense and negative impact, or side effects, associated with antifungal agents are two further issues of concern. Collectively, these problems are exacerbated by efforts to control resistant strains, which can evolve into a treadmill of higher dosages for longer periods. This cycle in turn, inflates cost of treatment, dramatically. A further problem is stagnation in development of new and effective antifungal agents, especially for treatment of human mycoses. Efforts to overcome some of these issues have involved using combinations of available antimycotics (e.g., combination therapy for invasive mycoses). However, this approach has had inconsistent success and is often associated with a marked increase in negative side effects. Chemosensitization by natural compounds to increase effectiveness of commercial antimycotics is a somewhat new approach to dealing with the aforementioned problems. The potential for safe natural products to improve antifungal activity has been observed for over three decades. Chemosensitizing agents possess antifungal activity, but at insufficient levels to serve as antimycotics, alone. Their main function is to disrupt fungal stress response, destabilize the structural integrity of cellular and vacuolar membranes or stimulate production of reactive oxygen species, augmenting oxidative stress and apoptosis. Use of safe chemosensitizing agents has potential benefit to both agriculture and medicine. When co-applied with a commercial antifungal agent, an additive or synergistic interaction may occur, augmenting antifungal efficacy. This augmentation, in turn, lowers effective dosages, costs, negative side effects and, in some cases, countermands resistance.
抗真菌化学增敏作用及其作用方式越来越受到关注。目前，抗真菌剂在农业和医学中的应用存在一些障碍。其中最主要的是对一种或多种抗真菌剂产生耐药性或交叉耐药性。与抗真菌剂相关的普遍高昂成本以及负面影响或副作用是另外两个令人担忧的问题。总体而言，为控制耐药菌株所做的努力加剧了这些问题，耐药菌株可能会演变成需要长期使用更高剂量药物的恶性循环。反过来，这个循环又大幅增加了治疗成本。另一个问题是新型有效抗真菌剂的研发停滞不前，尤其是在治疗人类真菌病方面。为克服其中一些问题所做的努力包括使用现有抗真菌剂的联合用药（例如，侵袭性真菌病的联合治疗）。然而，这种方法的效果并不稳定，而且往往伴随着副作用的显著增加。天然化合物的化学增敏作用以提高商用抗真菌剂的有效性是一种应对上述问题的新方法。安全的天然产物具有提高抗真菌活性的潜力这一现象已被观察到三十多年。化学增敏剂具有抗真菌活性，但单独使用时其水平不足以用作抗真菌剂。它们的主要功能是破坏真菌的应激反应，破坏细胞膜和液泡膜的结构完整性或刺激活性氧物质的产生，增强氧化应激和细胞凋亡。使用安全的化学增敏剂对农业和医学都有潜在益处。当与商用抗真菌剂联合使用时，可能会发生相加或协同相互作用，增强抗真菌功效。这种增强反过来又降低了有效剂量、成本、副作用，在某些情况下还能对抗耐药性。
