TITLE:
Update on the Fungal Biofilm Drug Resistance and Its Alternative Treatment
AUTHORS:
Karina Siow Yen Ng How Tseung, Jingjun Zhao
KEYWORDS:
Aspergillus fumigatus, Candida albicans, Biofilm, Antifungal Resistance, Combination Therapy, Traditional Chinese Medicine
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.4 No.5,
May
12,
2016
ABSTRACT: 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.