by Michael Spencelayh
Researchers from the UK have designed a test that will help in the search for new anti-malaria medicines.
Malaria is caused by parasites of the genus Plasmodium and causes over one million deaths per year. Plasmodium has a complex life cycle involving the host and an insect carrier, but a critical step is the invasion of red blood cells. The parasite attaches itself to the surface of the red blood cell, and then crosses the plasma membrane taking with it a bubble of membrane in which it replicates, protected from the host's immune system. This invasion is driven by a multi-protein motor complex in the parasite. Disrupting this motor could stall the invasion and interrupt the parasite life cycle, says Edward Tate at Imperial College London.
Tate and colleagues developed an assay to identify peptides that mimic part of myosin, one of the complex proteins, using fluorescent peptides. If the peptide mimic forms the complex with the parasite, the peptides undergo a shift in light emission, easily monitored by fluorescence spectroscopy.
'The continued rise of drug-resistant strains [of malaria] has resulted in an unrelenting biological arms race, and our method provides a new tool for screening potential inhibitors under high throughput,' explains Tate.
Eric Oldfield, a specialist in anti-parasitic drugs at the University of Illinois, US, comments, 'it is a very nice assay that opens up the way to designing peptide mimics that target invasion as novel anti-malarials.'
Although no significant inhibition of parasite growth was seen when tested on live parasites, Tate says this work paves the way for the design of peptide mimics that can replicate the key interactions of the protein complex and could help develop drug-like compounds that can disrupt the invasion motor.
Source: RSC