Fig 1.
The arsenal employed by C. glabrata to resist pharmaceutical interventions.
(A) The cell wall is the front line of battle between C. glabrata and antifungal drugs. Azoles target the plasma membrane, but resistance to azole drugs occurs through gain of function mutation in pdr1, which increases expression of drug efflux pumps. Polyenes bore into the plasma membrane paving the way for cytoplasmic contents, e.g., ions to leech into the extracellular space. Echinocandins target B-(1,3)-glucans. Resistance is consistently related to mutations in FKS genes, which normally govern B glucan synthesis. (B) Genomic flexibility drives adaptability and resistance in C. glabrata. Antifungal drug resistance correlates with increased telomere length and circularity of chromosomes. (C) Ploidy and aneuploidy drive genome plasticity by providing the framework through which the fungus makes genetic changes. (D) Biofilms adhere to biotic and abiotic surfaces, e.g., during mechanical ventilation. Due to varying cellular states and extracellular matrix, these entities are recalcitrant to therapeutics. Cells can slough off and result in systemic infection. This figure was created with Biorender.com.
Table 1.
Definitions of terms.