Fungal infections, also known as mycoses, occur when fungi invade and colonize tissues in the body. These infections can range from superficial skin conditions to severe, life-threatening systemic diseases. Unlike bacterial or viral illnesses, fungal infections present unique challenges for effective medical intervention, affecting millions of individuals globally each year.
Fungal Biology and Shared Characteristics
The fundamental reason fungal infections are difficult to treat lies in their cellular biology. Human cells and fungal cells both belong to the domain Eukarya, meaning they share complex internal structures like a nucleus and membrane-bound organelles. This close evolutionary relationship makes it challenging to develop medications that selectively target fungal cells without harming human cells. Many common antibiotics work by targeting features unique to bacteria, which are prokaryotes and structurally simpler. Drugs designed to disrupt fungal processes might inadvertently affect similar processes in human cells, leading to undesirable side effects. Therapies must walk a fine line, aiming to eradicate the fungal pathogen while preserving the host’s health.
Unique Fungal Defenses
Fungi possess several structural and physiological characteristics that enhance their resilience against both host defenses and antifungal treatments. A key defense is their rigid cell wall, a complex, multi-layered structure primarily composed of chitin and glucans, particularly β-(1,3) glucan, which provides mechanical strength and protection but can also hinder the penetration of antifungal drugs.
Many pathogenic fungi can also form biofilms, which are communities of cells encased in a protective extracellular matrix. Biofilms make fungi significantly more resistant to drugs and shield them from immune responses. Additionally, some fungi employ efflux pumps, which are specialized proteins that actively pump antifungal drugs out of the cell, further reducing the drug’s effectiveness.
Immune Evasion and Persistence
Fungi have evolved various strategies to interact with and evade the host’s immune system, contributing to their persistence within the body. Some fungi can alter their cell surface components, such as mannans, to shield highly immunogenic structures like β-1,3-glucan from immune recognition. This “masking” can prevent the immune system from mounting an effective response.
Certain fungal pathogens can survive and even replicate inside host immune cells, such as phagocytes, allowing them to remain hidden from other immune components. Fungi may also enter a dormant or metabolically inactive state, particularly in the form of spores. In this dormant state, their reduced metabolic activity makes them less susceptible to both immune clearance and antifungal agents, which often target active cellular processes.
Limited Treatment Options and Drug Resistance
The practical challenges in treating fungal infections include a limited arsenal of available medications. There are significantly fewer classes of antifungal drugs compared to antibiotics for bacterial infections. The main classes of antifungals include polyenes, azoles, and echinocandins.
These drugs often come with concerns regarding toxicity and side effects, which can necessitate careful monitoring and limit the dosage or duration of treatment. For example, amphotericin B, a polyene, is effective but known for potential kidney toxicity. A growing problem is antifungal drug resistance, where fungi develop mechanisms to withstand existing medications. Mechanisms of resistance include alterations in drug targets, overexpression of efflux pumps, and changes in sterol biosynthesis.