Researchers at the Indian Institute of Science (IISc) here have designed an antimicrobial peptide (AMP) that can quickly and effectively kill a notorious multi-drug-resistant Acinetobacter baumannii bacterium. This bacteria is number one on World Health Organization’s (WHO’s) ‘critical’ list of threats that urgently need new antibiotics because it is remarkably adept at developing drug resistance. It is also one of six species responsible for most of the hospital infections afflicting patients.
In a new study published in the journal Science Advances this month, IISc researchers used a bioinformatics approach to design a new short protein (peptide) called Omega76 that can kill A. baumannii by breaking down its cell membrane. So far, researchers have conducted experiments only on mice models. Infected mice treated with Omega76 had much better survival rates. The team also found that high doses of Omega76 given for prolonged periods did not produce any toxic effects. The team also found that Omega76 did not cause any significant damage to normal cells. As it is both safe and effective, it is considered a promising candidate for developing new antibiotics, an IISc release said citing the researchers.
Antibiotic resistance is a growing global threat, especially for millions of patients who develop infections in healthcare settings. The bacterium A. baumannii is particularly notorious for its ability to develop resistance very quickly and survive for long periods in hospitals.
“The significance of A. baumannii infection was not sufficiently understood earlier. It was regarded as just another bug in the environment. It has now become a major threat, especially in the intensive care units,” says Dipshikha Chakravortty, Professor at the Department of Microbiology and Cell Biology, and one of the senior authors of the study.
Antibiotics for such infections may soon become ineffective as resistance to even last-resort drugs such as carbapenems is on the rise. They are not entirely safe either. A drug called colistin, which is considered the last hope for multidrug-resistant infections, has been found to cause severe kidney damage, says first author and post-doctoral fellow Deepesh Nagarajan.
Recently, short polypeptides called antimicrobial peptides (AMPs) that kill bacteria by breaking down their membranes have shown promise as alternatives to conventional antibiotics.
Standard drugs act by blocking specific pathways or processes in bacterial cells, but bacteria can evolve to gain resistance against such drugs. “On the other hand, AMPs actually punch holes in the bacterial cell membrane. The chances of developing drug resistance are much lower because they act by multiple ways and cause actual physical damage (to the bacteria),” says Nagasuma Chandra, Professor at the Department of Biochemistry, and a senior author.
