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Updated: May 21, 2026
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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Polyene antibiotic that inhibits membrane transport proteins
Yvonne Maria te Welscher1, Martin Richard van Leeuwen, Ben de Kruijff
1Department of Biochemistry of Membranes, Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
Summary
Natamycin inhibits fungal growth by blocking amino acid and glucose transport, not by permeabilizing membranes. This ergosterol-dependent mechanism highlights the importance of sterol-protein interactions in fungal infections.
Area of Science:
- Mycology
- Biochemistry
- Molecular Biology
Background:
- Fungal infections pose a significant therapeutic challenge due to limited treatments and increasing antifungal resistance.
- Polyene antibiotics target the fungal plasma membrane by interacting with ergosterol, the primary fungal sterol.
- The precise mechanism of natamycin, a polyene antibiotic, has been unclear, as it does not cause membrane permeabilization.
Purpose of the Study:
- To elucidate the mode of action of natamycin in inhibiting fungal growth.
- To investigate the interaction of natamycin with ergosterol and its effect on membrane transport.
- To propose a general mechanism for polyene antibiotic action based on ergosterol-protein interactions.
Main Methods:
- Assessing the effect of natamycin on the growth of various yeasts and fungi.
- Measuring amino acid and glucose transport across the plasma membrane in the presence of natamycin.
- Investigating the specificity and reversibility of natamycin's inhibitory effects on transport proteins.
Main Results:
- Natamycin immediately inhibits amino acid and glucose transport in fungi.
- This inhibition is specific to ergosterol and is reversible.
- Natamycin's mode of action is distinct from membrane permeabilization caused by other polyenes.
Conclusions:
- Natamycin inhibits fungal growth by directly interfering with membrane transport proteins via ergosterol binding.
- Ergosterol-dependent inhibition of membrane proteins is proposed as a general mechanism for polyene antibiotics.
- These findings underscore the critical role of sterol-protein interactions in membrane protein function, even outside sterol-rich domains.
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