Researchers at the Indian Institute of Science (IISc) have designed a peptide, a compound that is made up of a chain of amino acids, that can poison a key enzyme used by disease-causing bacteria during their DNA replication process. This could be used to identify drugs to be used in combination with existing antibiotics to improve the effectiveness of treatments.
The peptide can even work in disrupting the DNA replication process of antibiotic-resistant bacterial species, causing a cascade of events that lead to cell death. Containing about 24 amino acids, the peptide inhibits an enzyme called topoisomerases which is also a target for most widely used antibiotics.
Topoisomerases binds with bacterial DNA to help it coil and uncoil during the DNA replication process. The peptide developed by IISc binds to this and stops it from functioning normally, causing the bacterial cells to die.
The compound is like a natural toxin called CcdB that is produced by certain bacteria and plasmids.
“The full length CcdB protein is large. It is not feasible to use it as a drug in its entirety,” Jayantika Bhowmick, lead author of the study who is a former PhD student at IISc’s Molecular Biophysics Unit and is currently a postdoctoral researcher at the University of Cambridge, said in a statement.
The team instead snipped out a small portion of the CcdB protein from its tail end and added a few more amino acids that would allow the new peptide to enter bacterial cells.
To test the effectiveness of the peptide, the researchers studied its effect on the growth of disease-causing bacterial like E. coli, Salmonella Typhimurium, Staphylococcus aureus and a multidrug resistant strain of Acinetobacter baumanii. They did this in both cell cultures and in animals.
“In most of the cases, we saw that the decline in the bacterial count in major organs following peptide treatment was higher than in the ciprofloxacin-treated group. That was pretty encouraging to us,” said Bhowmick.
Ciprofloxacin is one of the common antibiotics usually prescribed when treating intestinal infections.
The researchers reported that the peptide treatment caused an 18-fold reduction in bacterial load in the liver, compared to only a 3-fold reduction caused by ciprofloxacin. They reported that the peptide was relatively safe and did not cause toxic reactions in the animals.
