Molecular model of a lipid monolayer showing the fungal sterol ergosterol (yellow) interacting with the inserted antibiotic amphotericin (blue).
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Scientists at ISIS use neutron reflectivity and small-angle neutron scattering to uncover more about the mysterious drug amphotericin.
Amphotericin has been the first line of defence against fungal infections since the mid-1950s. Unfortunately, resistance to this drug is beginning to emerge, posing serious problems for AIDS and chemotherapy patients who often suffer potentially fatal fungal infections. Normally, replacement drugs would be sought by examining compounds with a similar mechanism of action. For amphotericin, though, this is difficult. It is established that the drug punches holes in cells, which makes them leaky and so causes them to die, but how it does this and why it causes more damage to fungal cells than human cells remains unclear.
Neutron reflectivity and small-angle scattering studies have been performed to study the effects of amphotericin on model human and fungal cell membranes, to find out why the drug is so selective.
Rather surprisingly, the drug is found to insert into both fungal and human cell membranes but the neutron studies also clearly show that it perturbs these two types of membranes in markedly different ways.
F Foglia, A Dabkowska, MJ Lawrence, DJ Barlow (King’s College London), R Barker (University of Bath), AE Terry, SE Rogers, AV Hughes, JRP Webster (ISIS)
Research date: August 2011
Contact: Dr DJ Barlow, dave.Barlow@kcl.ac.uk
Further reading: F Foglia et al., Biochim. Biophys. Acta 1808 (2011) 1574
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