Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Tamil Nadu, India.
Front Cell Infect Microbiol. 2022 May 25;12:887971. doi: 10.3389/fcimb.2022.887971. eCollection 2022.
Occurrence and intensity of systemic invasive fungal infections have significantly risen in recent decades with large amount of mortality and morbidity rates at global level. Treatment therapy lies on the current antifungal interventions and are often limited due to the emergence of resistance to antifungal agents. Chemosensitization of fungal strains to the conventional antimycotic drugs are of growing concern. Current antifungal drugs often have been reported with poor activity and side effects to the host and have a few number of targets to manifest their efficacy on the pathogens. Indiscriminately, the aforementioned issues have been easily resolved by the development of new intervention strategies. One such approach is to employ combinational therapy that has exhibited a great level of inhibitions than that of a single compound. Chemosensitization of pathogenic mycoses to commercial antifungal drugs could be drastically enhanced by co-application of chemosensitizers along with the conventional drugs. Chemosensitizers could address the resistance mechanisms evolved in the pathogenic fungi and targeting the system to make the organism susceptible to commercially and clinically proven antifungal drugs. However, this strategy has not been overreached to the greater level, but it needs much attention to fight against not only with the pathogen but combat the resistance mechanisms of pathogens to drugs. Natural compounds including plant compounds and microbial proteins act as potential chemosensitizers to break the resistance in mycoses. , a filamentous fungus, is known to produce a cysteine rich extracellular protein called as antifungal protein (AFP). AFP has shown enhanced efficacy against several filamentous and non-filamentous fungal pathogens. On the basis of the reported studies on its targeted potential against pathogenic mycoses, AFP would be fabricated as a good chemosensitizer to augment the fungicidal efficacy of commercial antimycotic drugs. This paper reviews on breakthrough in the discovery of antifungal drugs along with the resistance patterns of mycoses to commercial drugs followed by the current intervention strategies applied to augment the fungicidal potential of drugs.
近年来，全球范围内系统性侵袭性真菌感染的发生率和强度显著上升，死亡率和发病率居高不下。治疗方法取决于当前的抗真菌干预措施，但由于抗真菌药物耐药性的出现，这些方法往往受到限制。真菌对常规抗真菌药物的化疗增敏作用越来越受到关注。目前的抗真菌药物通常报道活性差，对宿主副作用大，并且对病原体表现出疗效的靶点很少。毫不夸张地说，上述问题很容易通过新的干预策略得到解决。一种方法是采用联合治疗，其抑制作用比单一化合物大得多。通过同时应用化学增敏剂和常规药物，可显著增强致病真菌对商业抗真菌药物的化疗增敏作用。化学增敏剂可以解决致病真菌中进化出的耐药机制，并针对该系统使生物体对商业上和临床上已证明的抗真菌药物敏感。然而，这种策略并没有得到充分的重视，不仅需要对抗病原体，还需要对抗病原体对药物的耐药机制。天然化合物，包括植物化合物和微生物蛋白，可作为潜在的化学增敏剂，打破真菌感染中的耐药性。一种丝状真菌，已知能产生一种富含半胱氨酸的细胞外蛋白，称为抗真菌蛋白（AFP）。AFP 对几种丝状和非丝状真菌病原体表现出增强的疗效。基于其针对致病性真菌的靶向潜力的报道研究，AFP 将被制成一种良好的化学增敏剂，以增强商业抗真菌药物的杀菌效果。本文综述了抗真菌药物的发现突破以及真菌对商业药物的耐药模式，随后介绍了增强药物杀菌潜力的当前干预策略。
