Candida Biofilms: Threats, Challenges, and Promising Strategies

Abstract

Candida species are fungal pathogens known for their ability to cause superficial and systemic infections in the human host. These pathogens are able to persist inside the host due to the development of pathogenicity and multidrug resistance traits, often leading to the failure of therapeutic strategies. One specific feature of Candida species pathogenicity is their ability to form biofilms, which protects them from external factors such as host immune system defenses and antifungal drugs. This review focuses on the current threats and challenges when dealing with biofilms formed by Candida albicans, Candida glabrata, Candida tropicalis, and Candida parapsilosis, highlighting the differences between the four species. Biofilm characteristics depend on the ability of each species to produce extracellular polymeric substances (EPS) and display dimorphic growth, but also on the biofilm substratum, carbon source availability and other factors. Additionally, the transcriptional control over processes like adhesion, biofilm formation, filamentation, and EPS production displays great complexity and diversity within pathogenic yeasts of the Candida genus. These differences not only have implications in the persistence of colonization and infections but also on antifungal resistance typically found in Candida biofilm cells, potentiated by EPS, that functions as a barrier to drug diffusion, and by the overexpression of drug resistance transporters. The ability to interact with different species in in vivo Candida biofilms is also a key factor to consider when dealing with this problem. Despite many challenges, the most promising strategies that are currently available or under development to limit biofilm formation or to eradicate mature biofilms are discussed.

Candida biofilm production is associated with higher mortality in patients with candidaemia

“…A population‐based surveillance from Italy revealed that biofilm production in Candida isolates is significantly associated with central venous or urinary catheter use and administration of total parenteral nutrition in the host patient . Biofilm formation is a key virulence factor for Candida species; it serves as a focus in bloodstream infections, protects the fungal cells against the immune response; furthermore, the presence of biofilms is associated with reduced susceptibility to antimicrobial agents . Until recently, data on the clinical impact of Candida biofilm on mortality were scarce and there were more contradictions than answers due to the diverse experimental settings and variable patient populations .…”

“…8 Biofilm formation is a key virulence factor for Candida species; it serves as a focus in bloodstream infections, protects the fungal cells against the immune response; furthermore, the presence of biofilms is associated with reduced susceptibility to antimicrobial agents. 9 Until recently, data on the clinical impact of Candida biofilm on mortality were scarce and there were more contradictions than answers due to the diverse experimental settings and variable patient populations. [10][11][12] Several studies drew attention to the problems possibly arising from the variability of biofilm detection methods and the poorly standardised cut-off points to distinguish biofilm-producer isolates from strains with low biofilm production capability.…”

Genetic and behavioral adaptation ofCandida parapsilosisto the microbiome of hospitalized infants revealed byin situgenomics, transcriptomics and proteomics

“…Biofilm formation is an important virulence factor of Candida infections (Cavalheiro et al 2018). Infant 06 had a documented Candida blood infection, and such infections are commonly systemic (Mavor et al 2005).…”

Pediatric Giant Cerebral <b><i>Candida</i></b> Abscess: A Case Report

“…Of these patients, 52–64% develop invasion in the central nervous system by candidiasis. The most common pediatric neurosurgical opportunistic infections of Candida develop during antibiotic resistance in bacterial shunt infections and use of broad-spectrum cephalosporin or carbapenem in ventriculitis [3, 9, 10]. No organism reproduced in the surgical aspirate culture and C. albicans was detected in the pathology assessment of the capsule taken with excision.…”