New generation of antibiotics may lie with small peptides

Date: Mar-26-2014As 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




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