Candida Auris: How Do They Become More Resistant to Antifungal Drugs and Other Antibiotics?

Candida auris is a type of yeast that can cause serious infections in humans, especially in hospital and nursing home patients with weakened immune systems.

It is also a major public health concern because it is often resistant to multiple antifungal drugs that are commonly used to treat fungal infections.

In some cases, Candida auris infections have been resistant to all four classes of antifungal drugs: azoles, polyenes, echinocandins, and flucytosine, as per CNBC.

How does this fungus become so strong, and what can researchers and physicians do to combat it?

The mechanisms of fungal drug resistance

(Photo : FRANCOIS LO PRESTI/AFP via Getty Images)

Fungi have evolved various mechanisms to overcome the effects of antifungal drugs. Some of these mechanisms are specific to Candida auris, while others are shared by other fungi. Here are some of the main ways that fungi develop drug resistance:

Hiding in biofilms: A biofilm is a complex mixture of sugars, proteins, DNA, and cells that forms on surfaces and protects the cells from environmental stressors, such as drugs and immune system attacks.

Candida auris and other fungi can form biofilms on medical devices, such as catheters and artificial joints, and on human tissues, such as skin and mucous membranes.

Biofilms make it harder for drugs to reach and kill the fungal cells, and also allow the cells to exchange genetic material that may confer resistance, as per CDC.

Building stronger cell walls: The cell wall is a structure that surrounds the fungal cell and helps maintain its shape and integrity.

It is composed of several types of polysaccharides, such as chitin and beta-glucan. Some antifungal drugs, such as echinocandins, target the cell wall by inhibiting the synthesis of beta-glucan.

However, some fungi can increase the production of chitin or other polysaccharides to compensate for the loss of beta-glucan and strengthen their cell wall, as per Phys.org.

Changing drug targets: Antifungal drugs work by binding to specific molecules or structures in the fungal cell that is essential for its survival or growth.

For example, azoles inhibit an enzyme called lanosterol 14-alpha-demethylase (ERG11), which is involved in the synthesis of ergosterol, a component of the fungal cell membrane.

However, some fungi can mutate or modify their drug targets so that they are less affected by the drugs. For example, Candida auris can alter the structure or expression of ERG11 or increase the production of ergosterol precursors to reduce the impact of azoles.

Pumping out drugs: Some fungi have efflux pumps that can expel foreign substances from their cells. These pumps can also remove antifungal drugs before they can exert their effects.

For example, Candida auris can overexpress efflux pumps such as CDR1 and CDR2 (candida drug resistance genes) or MDR1 (multidrug resistance gene) to decrease the accumulation of azoles or other drugs inside their cells.

Also Read: US Fungus Outbreak: Deadly Candida Auris Fungi Spreads in 28 States [CDC Warns] 

The strategies to overcome fungal drug resistance

Fungal drug resistance poses a serious challenge to the treatment and prevention of Candida auris and other fungal infections. However, there are some strategies that researchers and physicians can use to overcome this problem:

Developing new antifungal drugs: One way to combat fungal drug resistance is to discover new compounds or classes of drugs that have novel modes of action or target new pathways in the fungal cell, as per Pubmed.

For example, researchers are exploring the potential of peptides, nanoparticles, immunotherapy, or natural products as alternative or complementary antifungal agents.

Improving existing antifungal drugs: Another way to combat fungal drug resistance is to optimize the efficacy or safety of existing drugs by modifying their structure, formulation, delivery, or combination.

For example, researchers are testing new ways to enhance the penetration or stability of echinocandins in biofilms or to reduce the toxicity or interactions of polyenes.

Implementing antifungal stewardship: A third way to combat fungal drug resistance is to improve the appropriate use of antifungal drugs by following evidence-based guidelines and protocols for the diagnosis, selection, dosing, duration, and de-escalation of antifungal therapy.

Antifungal stewardship also involves educating healthcare personnel and patients about the appropriate use and potential harms of antifungal drugs.

Preventing and controlling fungal infections: A fourth way to combat fungal drug resistance is to reduce the incidence and transmission of fungal infections by implementing infection prevention and control measures, such as screening and isolating high-risk patients, improving hand hygiene and environmental cleaning, and reducing the use of invasive devices and immunosuppressive agents.

Related article: Deadly, Drug-Resistant Fungus Arrives in US: Fast Facts About Candida Auris