TABLE 3.
Potential molecular targets of amphotericin B resistance in A. terreus and non-A. terreus moldsa
| Potential target(s) | Comments |
|---|---|
| Cell membrane ergosterol | The role of ergosterol as resistance mechanism is unclear, as the content of ergosterol was similar for two species, ATR and polyene-susceptible A. fumigatus. |
| ATR and ATS showed the same level of ergosterol content. | |
| Cell wall composition | A. flavus resistant to amphotericin B showed an altered cell wall composition, and an increased β-1-3-glucan content was detected in the mutant strain. |
| In a study of protoplasts from A. fumigatus, ATR and ATS showed no significant differences. | |
| Mitochondrial functions | ATS displayed a 3-fold increase in O2 consumption compared to ATR. |
| ATS showed an elevated mitochondrial DNA content (23%) compared to ATR. | |
| Amphotericin B resulted in an upregulation of mitochondrial genome content in ATS, whereas it was decreased in ATR. | |
| Oxidative stress pathways | Catalase production is higher in ATR than in A. fumigatus. |
| Amphotericin B mediated elevated ROS levels in ATS in comparison to ATR. | |
| NAC rescued amphotericin B-induced ROS increase as well as amphotericin B tolerance in ATS. | |
| AA showed contrasting results. | |
| Molecular chaperone machinery | ATS showed only slightly increased HSP90 and HSP70 basal levels; ATR showed a strong reaction upon amphotericin B treatment, while ATS did not. |
| HSP70 member SSB was up-regulated in ATR by amphotericin B exposition in a 2D proteome analysis. | |
| Western blot experiments revealed that ATR exhibited high basal levels of SSA and SSB HSP70 proteins. | |
| Amphotericin B resulted in a robust induction of HSP70 in ATR in comparison to ATS. | |
| Trichostatin A was particularly active against ATR. | |
| HSP90 inhibitors resulted in significant improvement in amphotericin B activity against ATR; MICs decreased from 32 to 0.38 mg/liter. |