New generation of antibiotics may lie with small peptides
As drug-resistant bacteria - or "superbugs" - get stronger and we run out of current antibiotics to kill them, the pressure to find new types of effective drugs increases. Now, a team in Germany suggests small peptides - which can attack bacteria in several different ways - have the potential to form a new generation of antibiotics.
A new study published in the Proceedings of the National Academy of Sciences, PNAS, and led by researchers from Ruhr University Bochum (RUB), shows how peptides - short chains of amino acids that are smaller than proteins - may be developed to attack bacteria cells without harming human cells, while also making it difficult for the pathogens to develop resistance to them.
Previous studies have already shown that many antimicrobial peptides interact with the cell membrane of bacteria, killing them via this route.
But to authorize new drugs, federal authorities need detailed information about the underlying biology and assurances that the way the new drug attacks pathogen cells does not harm human cells.
The team at RUB has been studying a peptide called MP196, which represents a group of very small, positively charged peptides - cationic peptides - made of between four and 10 amino acids.
They already knew from previous research that MP196 could fight various bacteria, including some that are multi-drug resistant - but it was not clear how it did it.
With their new study, the team showed that MP196 interferes with proteins in the cell membrane of bacteria, and in doing so, disrupts two important cell processes: the biosynthesis of the cell wall and cell respiration.
Peptide disrupts bacterial cell respiration and physical integrity
By disrupting the biosynthesis of the cell wall, the peptide undermines the physical integrity of the bacterial cell, and by interfering with cell respiration, it disrupts production of ATP, the molecule that stores energy used by the cell. Less ATP means the bacterial cell is less able to make the big molecules it needs to grow and flourish.
Because of the nature of these disruptions, the team suggests it will also be difficult for the bacteria to develop resistance to peptides like MP196.
As part of the study, the researchers also discovered ways the bacterial cell responds to attack from the peptide. They write:
"We describe a bacterial survival strategy in which mechanosensitive channels in the bacterial membrane establish osmoprotection against membrane-targeting bacteriolytic peptides."
Peptide does not affect human cells
They are confident that MP196 offers a starting point for developing new drugs that attack certain classes of bacteria without damaging human cells, and their findings go a long way to help such development.
They explain that to attack the membrane of the bacterial cell, MP196 needs the presence of certain fatty acids that only occur in that class of bacteria - they are not present in human cells.
The study forms part of the Innovative Antibiotics from NRW (InA) project that is co-funded by the State of North Rhine-Westphalia and the "Investing in your Future" European Union's European Regional Development Fund.
Meanwhile, Medical News Today recently reported a study where researchers in Belgium discovered antibiotic resistance genes in viruses in 700-year-old human feces. As the feces predate the advent of antibiotics by several centuries, the researchers suggest this shows that the human gut has remained largely unchanged in that time.
Written by Catharine Paddock PhD
Copyright: Medical News Today
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