Future directions for anti-biofilm therapeutics targeting Candida

Abstract

While proliferating in its most common mode of growth, a biofilm, Candida spp. exhibit increased resistance to available antifungal agents. These adherent communities are difficult to eradicate and often responsible for treatment failures. New therapies are urgently needed to treat a variety of Candida biofilm infections in the medical setting. This review discusses the medical relevance of Candida biofilms, the drug resistance associated with this mode of growth, and approaches to combat these resilient infections.

Keywords::

• amphotericin B
• antifungal
• azole
• biofilm
• Candida
• echinocandin
• lock therapy
• matrix
• resistance

Financial & competing interests disclosure

The author's research is supported by a Burroughs Wellcome Fund Career Award for Medical Scientists. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Candida, one of the most common fungal pathogens, frequently grows as a biofilm adherent to a medical device or other surface.

• Candida biofilms exhibit increased resistance to antimicrobial therapies, including all available antifungal agents.

• The drug resistance of Candida biofilms is multifactorial. Contributing mechanisms include the presence of an extracellular matrix, increased activity of efflux pumps, increased cell density and induction of stress responses.

• Animal studies show that high doses of antifungals, such as liposomal amphotericin B and echinocandins, have anti-biofilm activity when delivered locally as catheter lock therapy.

• Therapies targeting the fungal stress responses (calcineurin, heat shock protein 90) can augment the action of antifungal drugs.

• Natural products, such as carbohydrate-derived fulvic acid and saponins, are promising compounds for treatment of Candida biofilms.

• A combination of high-throughput screens and animal models of Candida biofilm infection will be important for identifying and testing novel antifungals.