IISc peptide can kill antibioticresistant bacteria

NT Correspondent

Bengaluru: Researchers at the Indian Institute of Science (IISc) have designed a short peptide capable of poisoning a key enzyme in disease-causing bacteria, including some of the most deadly and antibioticresistant species.

Made from a short stretch of about 24 amino acids, the peptide mimics the action of a natural toxin which inhibits a class of enzymes called topoisomerases, according to Bengaluru-based IISc.

These enzymes play a crucial role in unspooling and re-coiling bacterial DNA during replication and protein synthesis. They are an attractive target for antibiotics because the ones in bacteria are very different from those in humans, an IISc release said on Thursday.

Among the most widely used antibiotics are fluoroquinolones such as ciprofloxacin, which target these topoisomerases. However, overuse of these antibiotics around the world has led to the alarming rise of antibiotic-resistant bacteria, prompting scientists to pursue alternative strategies and molecules.

Topoisomerases form a covalent adduct – an intermediate complex – with the bacterial DNA, to coil or uncoil it.

The peptide developed by the IISc team binds to this adduct and "traps" it in place, kicking off a cascade of events that lead to cell death, explains Raghavan Varadarajan, Professor at the Molecular Biophysics Unit (MBU), and one of the corresponding authors of the study published in 'EMBO Reports'.

This is similar to how a natural toxin called 'CcdB', produced by certain other bacteria and plasmids, works.