By Michael Edmonds
After a series of powerful broad spectrum antibiotics were developed in the 1980s many drug companies chose to cut back on antimicrobial research, assuming there would be no need for additional antibiotics. The rise in antibiotic resistant bacteria has demonstrated the folly of this decision, and companies are now scrambling to find new sources of antibiotics.
Dr J. Michael Conlon, at the United Arab Emirates University in Al Ain, Abu Dhabi, has discovered a novel and unexpected source of antimicrobial compounds; frogs. Like many other organisms, frogs produce antimicrobial peptides as part of their innate immune system. These peptides, which are found on the skin of frogs, are typically 8 to 48 amino acids long and able to form helical structures that are amphipathic (i.e. where one face is hydrophobic and the opposite face is hydrophilic). It is proposed that these peptides destroy invading cells by forming transmembrane pores or by breaking up the cell membranes.
Unfortunately, while these peptides effectively destroy invading cells they can also cause hemolysis — destruction of blood cells. Peptides are also quite quickly inactivated in the blood stream, which is why they often make poor drug candidates.
In order to overcome the hemolysis, Dr Condon has introduces some clever modifications to the peptides. Bacterial cells possess membranes with a higher percentage of negatively charged groups called phospholipids when compared to mammal cells. So Dr Condon has modified the structure of one antimicrobial frog peptide, temporin-DRa, by replacing one of the neutral amino acids with positively charged lysine, assuming that the positively charged lysine with be preferentially attracted to the negatively charged bacterial membranes. The result is a peptide with the same antimicrobial activity of temporin-DRa but with no hemolysis.
Dr Condon’s research group has performed similar amino substitutions on a range of other antimicrobial amphibian peptides resulting in several promising compounds. These compounds have demonstrated the potential for use in the treatment of fungal and bacterial infections including MRSA (Methicillin-resistant Staphylococcus aureus). While the tendency of peptides to be quickly inactivated in the bloodstream means that these new compounds are likely to be best suited for topical treatment, further modifications may provide compounds suitable for intravenous or even oral use.
Rovner, S. L. (2010), Frogs Inspire new Antimicrobials, Chemical and Engineering News, September 13, pg 36-37.
Michael Edmonds is an educator, researcher and manager at Christchurch Polytechnic Institute of Technology. He has strong interests in the communication and promotion of science.