Scientists from Novozymes have now found the mechanism by which plectasin, an anti-microbial peptide, kills bacteria that cause severe infections in humans.
Peptide antibiotics such as plectasin have retained antibiotic activity throughout evolution. The new knowledge shows that plectasin and other related peptides from invertebrates such as flies and mussels, targets the ‘Achilles heel’ of bacteria. Basically it binds and sequesters a precursor used in the cell-wall biosynthesis. As the bacteria cannot live without the cell-wall they are rapidly killed.
Experiments with plectasin show that it is very difficult for bacteria to develop resistance towards it. Bacteria truly resistant to Vancomycin, one of the antibiotics of choice in combating resistant bacteria and which also binds the same precursor, are still sensitive towards plectasin, making it a promising new alternative to resistant infections.
The groundbreaking results have been published in the May 28 issue of the internationally renowned journal Science.
“When we originally identified plectasin we knew that it was a breakthrough for research into antimicrobial peptides,” said Per Falholt, Novozymes’ executive vice president for Research & Development. “This new knowledge confirms it. We now know why it is almost impossible for bacteria to provoke resistance against plectasin.”
Till now it has been anticipated that plectasin like other peptides acts on and disintegrate the membrane making the bacteria collapse. Hans-Henrik Kristensen, one of the scientist behind the new discovery said they set out to determine how exactly plectasin kills the bacteria because several observations suggested that it would be different. “What we know now is that plectasin acts by directly binding the bacterial cell-wall precursor. This explains the specificity of plectasin and the observation that much larger doses of plectasin compared to other membrane-active peptides can be safely administered” he said.
Combating severe infections
Plectasin works on bacterial infections that are resistant to conventional antibiotic. An improved derivative out licensed to Sanofi-Aventis, NZ2114, even targets severe diseases like pneumonia, endocarditis, meningitis and blood poisoning caused by bacteria like Streptococcus andStaphylococcus which are resistant to all existing antibiotics. This will make it an effective new weapon for doctors, who are currently powerless in the face of these infections.
According to the WHO antibiotic resistance is a major cause of concern. The problem of resistance is global and in developing countries even common bacterial infections are showing resistance. In countries with poor healthcare services and where people cannot necessarily afford hospital care, the growing inability of doctors to treat common infections has serious implications for public health.
“As the dangers of antibiotic resistance continue to grow throughout the world, it is important to constantly look for new substances and methods to combat potentially deadly infections,” said Per Falholt who also said that the company has more peptides in the pipeline: “Our strong technology platform allows us to screen for new peptides very efficiently and we have identified others which are targeted at completely different types of infections.”
Plectasin also recognized by Nature
Novozymes identified Plectasin in 2002 but it was not until 2005 when Nature magazine published an article about the peptide that it became well-known by the global scientific community. In 2008 Novozymes granted Sanofi-aventis an exclusive worldwide license for the development, registration and commercialization of Plectasin.