Table 3.

Major classes of anti-fungal drugs and mechanism of resistance in Candida species (Kanafani and Perfect, 2008; Pfaller, 2012; Vandeputte et al., 2012; Morace et al., 2014; Patil et al., 2015; Sanguinetti et al., 2015; Sanglard, 2016; Hampe et al., 2017).

Anti-fungal	Mechanism of action	Mechanism of resistance development
Azoles	Inhibit the target enzyme lanosterol 14-a-sterol demethylase, which aids in the conversion of lanosterol to ergosterol (an important component of the fungal cell membrane), resulting in accumulation of the toxic product 14-a-methyl-3,6-diol	Development of active efflux pumps (facilitated by up regulation of the CDR1, CDR2 and MDR1 genes) Prevents binding to the target enzyme lanosterol C14a-demethylase site (mutations in the ERG11 gene) Target enzyme up-regulation (higher intracellular ERG11p concentrations Prevents the formation of 14a-methyl-3,6-diol (a toxic product) from 14a-methylfecosterol and enables functional membranes (mutation of the ERG3 gene) Gain of function mutations in Mrr1, Tac1 and Upc2 (zinc cluster transcription factors)
Polyenes	Formation of porin channels leading to loss of transmembrane potential and impaired cellular function	Defects in the ERG3 gene Increased catalase activity
Echinocandins	Inhibit the synthesis of b-1,3-D glucan, which is an integral component of the fungal cell wall	Point mutations in the Fks1 gene Increase in chitin synthesis in Candida species Paradoxical effect
Pyrimidine analog	Inhibits cellular DNA and RNA synthesis	Mutation in cytosine permease Defects in flucytosine metabolism through mutations in cytosine deaminase or uracil phosphoribosyl transferase (FUR1 gene mutations)