Referring to the recent article on antimicrobial peptides which featured an interview with Dr Tatjana Heinrich, who leads the Antimicrobial Discovery group of Phylogica - I was intrigued by Dr Heinrich's statement that she’s most encouraged by the evidence that antimicrobial peptides can rejuvenate traditional antibiotics to which bacteria have become resistant, essentially making them effective again. (1)
This combination approach sounds similar to that used in the recent cancer pilot study, where Phylomer peptide fusions were combined with and shown to significantly boost the potency of existing cancer drugs. But what is the evidence about antimicrobial peptides “rejuvenating” existing antibiotics to which Dr Heinrich refers?
A check revealed some recent research from the UK in which the antimicrobial peptide plectasin was tested as a synergistic agent in combination with traditional antibiotics. (Plectasin is a peptide derived from fungi that grows on horse dung. Its antimicrobial properties were discovered by Novozymes in 2002. NZ2114, a derivative of plectasin, was subsequently licensed in 2008 to Sanofi, but further research on the drug seems to have been discontinued.)
Plectasin by itself had already been demonstrated to have antimicrobial activity against many Gram-positive bacteria including drug resistant Streptococci and Staphylococci. The recent UK study shows that the peptide also demonstrates significant synergistic activities when combined with amoxicillin, penicillin, flucloxacillin, gentamicin, neomycin or amikacin, both in vitro and in vivo.
One of the reasons for the emergence of antibiotic resistance is believed to be the poor permeability of bacterial cell envelope to antimicrobial agents. Plectasin’s efficacy is attributed by the study authors to its ability to target the bacterial cell membrane.
The study authors conclude that there are four important positive clinical implications from their findings.
That other similar peptides will most likely be beneficial above and beyond their direct anti-microbial properties.
Synergistic combinations improve the effectiveness of antibiotics in terms of faster action and lower relapse.
Highly resistant bacteria, such as MRSA, which can be difficult to treat, may now be successfully eliminated from culture with combination therapy.
Combination therapy has the potential to reduce the therapeutic dose of antibiotics such as aminoglycosides, thus minimizing their toxic side effects.(2)
The first conclusion appears to have already been supported. Results have been published in recent months from further studies conducted by some of the same researchers. Two studies investigated the synergistic action of the peptides novicidin and PA-KKkK against Gram-negative antibiotic-resistant E. Coli and Enterobacteriaceae. Both studies provide evidence that these peptides are also effective as “antibiotic enhancers”. (3,4)
I wonder if this is the direction of Phylogica’s collaborative research with Genentech – to find peptides with direct antimicrobial properties that can enhance the action of existing antibiotics?
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