摘要
Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims to these fungi, with a mortality rate rising drastically over the past decades. This is in correlation with the fact that conventional antifungals are no longer capable of completely eradicating the disease, or if so, high doses are usually required to do so, leading to eventual resistance to those drugs and severe side effects. High drug resistance is in association with the discovery that these opportunistic pathogens have the ability to develop a multicellular complex, known as biofilm. Biofilms prevent drugs from reaching the fungal cells by sequestering them in their extracellular matrix. Other factors such as extracellular DNA, persister cells or heat shock protein 90 (Hsp90) also play a role in biofilm and contribute to drug recalcitrance. With the discovery of new antifungals lagging behind, scientists focused on other more profitable ways to counteract this phenomenon. Combination of two or more antifungals was found effective but came with serious drawbacks. Natural plant extracts, such as traditional Chinese medicine have also been demonstrated in vitro to possess antimicrobial actions. Great interest was directed towards their use with conventional antifungal agents with a possibility of lowering the necessary concentration required to inhibit the growth of fungi. This review aims in understanding the different factors contributing to clinical drug resistance and evaluating the effect of combination therapy and natural products on those cases difficult to treat.
Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims to these fungi, with a mortality rate rising drastically over the past decades. This is in correlation with the fact that conventional antifungals are no longer capable of completely eradicating the disease, or if so, high doses are usually required to do so, leading to eventual resistance to those drugs and severe side effects. High drug resistance is in association with the discovery that these opportunistic pathogens have the ability to develop a multicellular complex, known as biofilm. Biofilms prevent drugs from reaching the fungal cells by sequestering them in their extracellular matrix. Other factors such as extracellular DNA, persister cells or heat shock protein 90 (Hsp90) also play a role in biofilm and contribute to drug recalcitrance. With the discovery of new antifungals lagging behind, scientists focused on other more profitable ways to counteract this phenomenon. Combination of two or more antifungals was found effective but came with serious drawbacks. Natural plant extracts, such as traditional Chinese medicine have also been demonstrated in vitro to possess antimicrobial actions. Great interest was directed towards their use with conventional antifungal agents with a possibility of lowering the necessary concentration required to inhibit the growth of fungi. This review aims in understanding the different factors contributing to clinical drug resistance and evaluating the effect of combination therapy and natural products on those cases difficult to treat.
