Peptide a forerunner to novel antibiotic class?
naturally-occurring protein that could represent a new class of
antibacterial to tackle the growing problem of antibiotic
resistance.
In developed countries, up to 60 per cent of hospital-acquired infections are due to drug-resistant microbes. The most recent of these to appear are vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). These hospital infections are now beginning to spread into the general community, at a time when pharmaceutical companies are reining back their spending on new anti-infectives.
The scientists, from the University of Lund, have developed a peptide fragment of cystatin C, a protein that occurs naturally in humans and other species as part of the defence against bacteria, fungi and viruses. Cystatin C is a member of a superfamily of cysteine serine protease inhibitors that have a wide range of functions in the body.
"The substance has been shown to be effective against infectious staphylococci, streptococci, enterococci, and pneumococci bacteria, which include many dangerous and more or less antibiotic-resistant strains," said Aftab Jasir, one of the researchers working on the project.
It also seems to have activity against some viruses, including polio and herpes viruses, something that makes it unique amongst anti-infective drugs developed to date.
Along with colleagues Claes Schalen and Anders Grubb, Jasir tested the peptide, called Cystapep 1, against a range of bacteria that are commonly encountered as hospital-acquired infections, and found that it had particularly good activity against MRSA and multiresistant coagulase-negative staphylococci (CNS).
As the latter infections are notoriously resistant to antibiotic treatment, the results suggest that Cystapep 1 is working though a different mechanism of action to other antibacterials. "We still do not know the target," she told DrugResearcher.com, although the team has shown that it is definitely not hitting the cell wall, ribosomes, DNA or other common antibacterial targets.
The peptide has also been modified to minimise its activity against the normal bacterial flora present in the gut, said Jasir. This means that it could avoid the side effects of other antibiotic classes, which kill gastrointestinal bacteria and allow the colonisation of other, sometimes pathogenic strains.
The team has also found little evidence of toxicity in animal models to date, with no cellular damage observed in ex vivo experiments, although Jasir stressed that there is still a lot of work to be done before the compound can start human trials.
Nevertheless, Cystapep 1 has many other properties that make it an attractive proposition for commercial development, according to Jasir. For example, it is a small peptide, easy to produce, and looks like it may be suitable for oral administration.
The researchers are hoping to enter into an initial partnership with a commercial enterprise to continue their studies on Cystapep 1's mechanism, and in time would like to license it out to a pharmaceutical company for further development.
A study on the peptide was recently published in Acta Patologica Microbiologica Immunologica Scandinavica (2003 Nov;111(11):1004-1010).
