Virology & Mycology
Open Access

Biofilm Formation and Drug Resistance in Viral and Fungal Coinfections

Cheryl Lim Mei Lin^{* *}Correspondence: Cheryl Lim Mei Lin, Institute of Environmental Microbiology and Pathogen Dynamics, University of Ljubljana, Slovenia, Email:

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Description

The interplay between viral and fungal pathogens in coinfections presents a formidable challenge to clinical management, particularly due to the emergence of biofilm-associated drug resistance. Biofilms—structured communities of microorganisms encased in a self-produced matrix—are predominantly associated with bacterial infections, but recent research has shed light on their formation and significance in fungal and even viral contexts, especially during coinfections. In immunocompromised patients, such as those undergoing organ transplantation, chemotherapy, or intensive care, the risk of coinfection is heightened. The simultaneous presence of viruses and fungi not only exacerbates disease severity but also promotes microbial persistence and resistance through synergistic interactions, many of which are mediated by biofilm formation.

Fungal species such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans are well-documented biofilm formers. These fungi attach to surfaces like medical devices, respiratory tissues, and vascular catheters, producing complex extracellular matrices that shield the embedded cells from antifungal agents and immune system attacks. In parallel, certain viruses, notably respiratory viruses such as influenza, RSV, and SARS-CoV-2, can predispose patients to fungal colonization by damaging mucosal barriers and modulating host immune responses. This viral-induced immunosuppression creates a favorable niche for fungal biofilm establishment, which is particularly problematic in the lungs, where invasive fungal infections are associated with high mortality.

Interestingly, recent studies have shown that some viruses can themselves associate with biofilms or indirectly stimulate biofilm development by altering the host environment or microbial signaling. For instance, influenza infection has been shown to promote Candida biofilm formation in the respiratory tract by modulating cytokine profiles and exposing extracellular matrix components that facilitate fungal adhesion. Similarly, SARS-CoV-2 has been linked to increased incidence of invasive fungal infections like COVID-19-associated pulmonary aspergillosis (CAPA), which frequently involve biofilm-driven resistance mechanisms. These synergistic effects between viruses and fungi worsen clinical outcomes and complicate treatment protocols.

One of the most alarming features of biofilm-associated infections is their profound resistance to antimicrobial therapy. Within biofilms, microbial cells exhibit up to 1000-fold increased resistance to drugs compared to their planktonic counterparts. This resistance arises from multiple mechanisms, including restricted drug penetration, altered metabolic states of cells within the biofilm, efflux pump activation, and protective interactions among species. In the context of viral and fungal coinfections, biofilm formation significantly impairs the efficacy of conventional antifungal agents such as azoles and echinocandins. Furthermore, the persistent viral infection can necessitate immunosuppressive treatments like corticosteroids, which further reduce host defenses and promote biofilm resilience.

The clinical implications of such coinfections are severe. Patients with biofilm-driven coinfections often exhibit prolonged hospital stays, higher rates of mechanical ventilation, and increased mortality. Treatment failure is common due to the recalcitrant nature of biofilms, and eradication typically requires combination therapy or mechanical removal of infected devices. Diagnostic challenges further complicate management; standard culture-based methods often fail to detect biofilm involvement, and distinguishing between colonization and true infection is particularly difficult in polymicrobial settings. Molecular diagnostic tools and imaging techniques, while more sensitive, are not yet widely available in many clinical settings.

Research efforts are now directed at disrupting biofilm integrity and preventing its formation in high-risk patients. Promising strategies include the use of biofilm-disrupting agents such as DNase, quorum-sensing inhibitors, and enzymes that degrade extracellular matrix components. Nanoparticle-based delivery systems are also being explored to enhance drug penetration and retention within biofilms. From a preventive standpoint, improved infection control practices, careful management of immunosuppression, and early antiviral interventions may help reduce the incidence of coinfection-driven biofilm formation.

In conclusion, the phenomenon of biofilm formation in viral and fungal coinfections represents a critical frontier in infectious disease research and clinical care. It underscores the complexity of host-pathogen interactions and highlights the limitations of existing antimicrobial therapies in the face of microbial synergy. As biofilm-associated drug resistance continues to drive morbidity and mortality, especially in immunocompromised populations, a multifaceted approach combining early diagnosis, innovative therapeutics, and interdisciplinary care will be essential.