Table 3.
Detailed characteristics of Candida persister cells.
| Feature | Molecular/physiological basis | Effect on antifungal susceptibility | Associated pathways/biomarkers | References |
|---|---|---|---|---|
| Non-heritable Drug Tolerance | Persisters arise from transient metabolic/physiological states rather than stable ERG or drug-target mutations | Survive concentrations >100× MIC; can regrow after treatment stops | Phenotypic heterogeneity; transient downregulation of growth pathways | Lewis, 2010; Delarze and Sanglard, 2015 |
| Biphasic Killing Kinetics | Majority population rapidly killed, small persistent subpopulation remains,plateau in killing curve | Leads to treatment failure despite high-dose fungicidal drugs | Classic persister phenotype indicator | LaFleur et al., 2006; Wuyts et al., 2018 |
| Metabolic Dormancy/Slow Growth | decrease Glycolysis, increase gluconeogenesis; accumulation of energy-storage molecules (trehalose, glycogen) | Fungicidal drugs are ineffective on non-growing cells | Trehalose synthase, glycogen synthase upregulation | Kuczyńska-Wiśnik et al., 2015; Wuyts et al., 2018 |
| Activation of Stress Response Pathways | Hsp90 protects key signaling proteins; calcineurin stabilizes cell-wall repair; antioxidants reduce ROS toxicity | Enhances survival under azoles, echinocandins, polyenes | Hsp90–calcineurin axis; SODs, catalases | Li et al., 2021; O’Meara et al., 2017; Gong et al., 2017 |
| Oxidative Stress Resistance | Increased ROS-detoxification enzymes and redox buffering | Polyenes and some azoles generate ROS; persisters survive | SOD2, catalase (CAT1), glutathione pathways | da Silva et al., 2021 |
| Cell-Wall & Membrane Remodeling | Increased chitin synthesis, altered lipid composition | Reduces drug entry; compensates for echinocandin damage | Chitin synthase, ERG gene modifications | Robbins et al., 2011 |
| Strain- and Condition-Dependence | Persisters appear only in some C. albicans strains and specific biofilm models | Not all isolates form persisters experimental variability | Depends on substrate, nutrient conditions, and drug regimen | Denega et al., 2019 |
| Matrix-Associated Protection | Persisters are often found deep inside biofilm matrix niches | ECM limits drug penetration, facilitates persister survival | β-glucan-rich ECM microenvironments | Pierce et al., 2017; Nett and Andes, 2020 |
MIC, Minimum Inhibitory Concentration; Hsp90, Heat Shock Protein 90; ROS, Reactive Oxygen Species; SODs, Superoxide Dismutases; CAT1, Catalase 1; ECM, Extracellular Matrix.