Molecular mechanisms of fungal biofilm resistance. Antifungal drug resistance in fungal biofilms is both complex and multifactorial. The diagram illustrates the mechanisms of different class of antifungal agent action (azoles [AZL], polyenes [POL], and echinocandins [ECN]) and resistance: (a) the layer of ECM present in the biofilm shields the cells from antifungal agents by binding and reduced penetration; (b) the membrane transporter system ABC and MFS efflux pumps extrude antifungal molecules and reduce the intracellular concentration; (c) mutation in ERG, Cyp51, and FKS1 genes alters the drug target leading to cross-resistance; (d) antifungal pressure induces stress responses, such as the calcineurin signalling pathway, which is activated, and coping responses occur through upregulation of various signal transducers. On the right hand side, the table lists different resistance genes and their functions, and antifungal agents affected.
