A Novel Approach to Fighting Fungal Infection

Submitted by GAtherton on 18 September 2017

Antifungal drug strategies are in need of a rethink as current azole medication is gradually losing its efficacy with the rise in resistant fungal strains. It might even be true to say that any drug that is developed that disrupts the metabolism of a micro-organism sufficiently to kill it or slow it down enough to allow our immune systems to attack and remove the fungus is vulnerable to the development of resistance.

Chirkin et. al. have taken a new approach to killing fungal infections. They have developed a new generation of antifungal molecules that attack the fungus indirectly by enabling our immune system to target the microbe more effectively. The new molecule (ARM-F) recognises fungi and binds to the fungal cell wall in large numbers. The fungal cell wall is made of chitin and is completely unlike anything found in mammalian tissue so none of the new molecules will bind to the patient’s cells potentially making this strategy non-toxic.

Once bound the new molecule is bound it attracts antibodies that are already present in the patient’s bloodstream. These antibodies (called anti-DNP) are even thought to be found in the bloodstream of patients who are immunocompromised which is especially useful as this group of patients is very vulnerable to fungal infection. Once bound to the new molecule the fungus becomes more readily recognised by the patient’s phagocytic immune cells whereupon it is engulfed and destroyed.

The authors claim that as the new molecules are never internalised by the fungus it will be very difficult for the fungus to become resistant to this treatment strategy. It is also apparent that this treatment will be unaffected by the fungal mechanisms that render them resistant to existing antifungal drugs. We can also suggest that the use of this treatment alongside an existing antifungal drug may well increase the antifungal efficacy synergistically as each has a distinct target of attack and the action of some antifungals (e.g. caspofungin) exposes more fungal cell wall chitin to ARM-F’s.

Thus far the authors have proven the principle of this mode of attack in vitro by showing that ARM-F’s dramatically increase the recognition and phogocytosis of treated Candida cells by human neutrophils. In vivo model tests are likely to follow soon.