Future microbiology · 2026
Mechanisms and species-specific patterns of ECM-mediated antifungal resistance in Candida biofilms: a systematic review and exploratory quantitative synthesis.
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Tuan Dang Anh, Uyen Pham Vu Nhat
Аннотация
AIMS: To synthesize mechanistic evidence on how extracellular matrix (ECM) components of Candida biofilms contribute to antifungal resistance across species and antifungal drug classes.
MATERIALS AND METHODS: We conducted a PRISMA-guided systematic review with exploratory random-effects quantitative synthesis of peer-reviewed experimental studies evaluating ECM composition, matrix-associated regulatory pathways and antifungal susceptibility in Candida biofilms. Qualitative synthesis mapped ECM components and pathways, while harmonizable semi-quantitative data were summarized as directional modeled estimates.
RESULTS: Of 38 full-text records assessed, 33 primary studies were included in the qualitative synthesis and 25 contributed to the exploratory pooled analysis. Preservation or modulation of ECM-associated mechanisms showed a strong modeled directional association with reduced antifungal susceptibility (pooled modeled odds ratio: 4.28, 95% CI: 4.06-4.52). β-1,3-glucan was the most consistently supported sequestration scaffold, particularly for azoles and polyenes. Mannan-glucan complexes, matrix proteins, extracellular DNA and vesicle-associated lipids provided complementary structural and remodeling functions. Non-albicans Candida species, especially Candida glabrata and Candida auris, more often combined ECM protection with efflux-linked resistance.
CONCLUSIONS: ECM-mediated resistance in Candida biofilms is multilayered, species-dependent and drug-class specific. These findings support species-aware interpretation of biofilm-associated antifungal resistance and further development of ECM-directed adjunctive strategies.
MATERIALS AND METHODS: We conducted a PRISMA-guided systematic review with exploratory random-effects quantitative synthesis of peer-reviewed experimental studies evaluating ECM composition, matrix-associated regulatory pathways and antifungal susceptibility in Candida biofilms. Qualitative synthesis mapped ECM components and pathways, while harmonizable semi-quantitative data were summarized as directional modeled estimates.
RESULTS: Of 38 full-text records assessed, 33 primary studies were included in the qualitative synthesis and 25 contributed to the exploratory pooled analysis. Preservation or modulation of ECM-associated mechanisms showed a strong modeled directional association with reduced antifungal susceptibility (pooled modeled odds ratio: 4.28, 95% CI: 4.06-4.52). β-1,3-glucan was the most consistently supported sequestration scaffold, particularly for azoles and polyenes. Mannan-glucan complexes, matrix proteins, extracellular DNA and vesicle-associated lipids provided complementary structural and remodeling functions. Non-albicans Candida species, especially Candida glabrata and Candida auris, more often combined ECM protection with efflux-linked resistance.
CONCLUSIONS: ECM-mediated resistance in Candida biofilms is multilayered, species-dependent and drug-class specific. These findings support species-aware interpretation of biofilm-associated antifungal resistance and further development of ECM-directed adjunctive strategies.