Drug interaction between AmB and 5-FC against <i>A. fumigatus.</i>

<p>AmB: Amphotericin B, 5-FC: 5-Flourocytosine.</p><p>MICs of AmB and 5-FC alone and in combination against <i>A. fumigatus</i> in 3 separate experiments and calculated FIC values.</p

Perturbations in nucleotide metabolism do not alter the AmB susceptibility of <i>Aspergillus fumigatus</i>.

<p>E-Test analysis of <i>A. fumigatus</i> wt on AM3 medium alone or supplemented with 3.25 µg/mL MPA. (B) Checkerboard analysis to assess drug interaction between AmB and 5-FC against <i>A. fumigatus</i> using the following drug ranges; AmB 0.097 µg/mL to 50 µg/mL and 5-FC from 1.56 µg/mL to 100 µg/mL.</p

Perturbations in nucleotide biosynthesis sensitize <i>Candida albicans</i> to AmB.

<p>E-Test analysis for AmB susceptibility of (A) <i>C. albicans</i> wt and <i>ura</i>⁻ mutant on AM3 medium (B) <i>C. albicans</i> wt on AM3 medium alone or supplemented with 3.25 µg/mL MPA (C) <i>C. albicans</i> wt and <i>ura</i>⁻ mutant supplemented with 20 µM uracil or 20 µM uridine.</p

AmB and MPA synergize against <i>C. neoformans</i>.

<p>Assay range of concentrations for AmB is 0.0009 µg/mL to 0.5 µg/mL and for MPA is 0.45 µg/mL to 30 µg/mL. Well A12 is the sterility control (SC) and wells H1 and H12 are growth controls (GC) for MPA and AmB respectively.</p

Drug interaction between AmB and MPA in <i>C. albicans.</i>

<p>AmB: Amphotericin B, MPA: Mycophenolic acid.</p><p>MICs of AmB and MPA alone and in combination against <i>C. albicans</i> in 3 separate experiments and calculated FIC values.</p

MPA potentiates the killing of <i>C. neoformans</i> by AmB.

<p>Time kill assay of <i>C. neoformans</i> in the presence of AmB at either 0.03 µg/mL or 0.06 µg/mL of AmB alone or in combination with 30 µg/mL MPA. CFU were enumerated from triplicate plates. The graph represents mean CFU +/− SEM (****<i>p</i><0.0001, ***<i>p</i><0.001, **<i>p</i><0.01, *<i>p</i><0.05).</p

A <i>C. neoformans ura</i>⁻ strain is hypersensitive to AmB.

<p>(A) E-Test for AmB susceptibility of <i>C. neoformans</i> wt, <i>ura</i>⁻ mutant and <i>ura</i>⁻ strain complemented with the wild type <i>URA5</i> gene on AM3 medium (B) E-Test for AmB susceptibility of <i>C. neoformans</i> wt and <i>ura</i>⁻ mutant on AM3 medium supplemented with 20 µM uracil and 20µM uridine.</p

AmB and MPA or 5-FC exhibit positive interactions against <i>Candida albicans</i>.

<p>(A) Checkerboard analysis of drug interaction between AmB and MPA against <i>C. albicans.</i> Assay range of concentrations for AmB was 0.0009 µg/mL to 0.5 µg/mL and MPA was 0.45 µg/mL to 30 µg/mL. (B) Checkerboard analysis of drug interaction between AmB and 5-FC against <i>C. albicans</i>. The range of drug concentration used for AmB was the same as in previous experiments, for 5-FC the range was 0.015 µg/mL to 0.96 µg/mL.</p

Inhibition of guanosine biosynthesis sensitizes <i>C. neoformans</i> to AmB.

<p>(A) E-Test of <i>C. neoformans</i> wt on AM3 medium (B) AM3 medium supplemented with 3.25 µg/mL MPA and (C) E-test analysis for AmB susceptibility of <i>C. neoformans</i> wt on AM3 supplemented with 3.25 µg/mL MPA and 20 µg/mL exogenous guanine.</p

Drug interaction between AmB and 5-FC in <i>C. albicans.</i>

<p>AmB: Amphotericin B, 5-FC: 5-Flourocytosine.</p><p>MICs of AmB and 5-FC alone and in combination against <i>C. albicans</i> in 3 separate experiments and calculated FIC values.</p