Table 1. Selection of inhibitors and inducers of the miconazole-affected pathways and combinatory action with miconazole against C. albicans biofilms determined by FICI calculation.
Process or protein | Effect in miconazole RNAseq data | Compound | BEC50 | Activity in combination with miconazolea |
---|---|---|---|---|
Inhibitors | ||||
Sterol biosynthetic process | Induced | Simvastatin | 1.4 mM | S |
Secreted aspartic-type proteinases | Induced | Saquinavir mesylate | >500 μM | I |
Lipases | Induced | Orlistat | >1 mM | I |
Glyoxylate cycle | Induced | Itaconate | >2 mM | I |
ETC | Repressed | Antimycin A | 570 μM | S |
CCCP | 73 μM | S | ||
Sodium azide | 8.6 mM | S | ||
Sphingolipid biosynthesis | Induced | Myriocin | >100 μM | I |
Alcohol dehydrogenase | Induced | Disulfiram | >500 μM | I |
Branched-chain amino acid (including leucine) biosynthesis | Induced | Chlorosulfuron | >1 mM | I |
Fe-S bonds (as in Leu1 and many mitochondrial respiratory enzymes) | Induced | Pyrithione zinc | 275 μM | S |
Tetrahydrofolate interconversion | Induced | Trimethoprim | >500 μM | I |
Inducers | ||||
Nicotinic acid transporter | Induced | Nicotinic acid | >1 mM | I |
Arginine biosynthesis | Repressed | Arginine | >10 mM | I |
Leucine biosynthesis | Induced | Leucine | >2 mM | I |
Citric acid cycle | Repressed | Sodium dichloroacetate | >1 mM | I |
N-acetylglucosamine transporter | Repressed | N-acetyl-D-glucosamine | >1 mM | I |
aS = Synergy (FICI < 0.5), I = Indifference (0.5 < FICI < 4), FICI = [CA/BEC50A] + [CB/BEC50B], in which BEC50A and BEC50B are the BEC50 values (biofilm eradication concentration resulting in 50% remaining biofilm metabolic activity) of compound A and B alone, while CA and CB are the concentrations of the drugs A and B at iso-effective combinations, respectively. Note that CB values were derived from the whole dose-response curves, whereas CA values represent the actual concentration of compound A in the checkerboard experiments.