Two new molecules capable of destroying bio-film forming bacteria have been developed by scientists at the Bengaluru-based Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR). The molecules performed better than conventional antibiotics in killing the bacteria during the dormant phase. Biofilms are communities of microorganisms that attach to each other and to surfaces and are able to act as barriers to antibiotics. When used in combination with existing antibiotics, the molecules reduced the microbial burden in the case of burns and surgical wounds.
The effect of these macromolecules on chronic biofilm causing pathogens like E. coli, Acinetobacter, Klebsiella were studied and the results were recently published in PLOS ONE.
Antibacterial activity
The researchers studied the effect of the compound on dormant state E. coli. “We tested on E. coli that reside in biofilms in a dormant condition. The new macromolecules killed the bacteria by targeting their cellular membrane, the protective layer present in both active as well as dormant state,” explains Dr. Divakara SSM Uppu at JNCASR and the first author of the article. Antibiotics become effective when the bacteria are in an active state.
While 100 microgram/mL of antibiotics (ampicillin and kanamycin) was required to partially kill the bacteria, a concentration of just 10 microgram/mL of the macromolecule was able to completely kill E. coli. “With the rise of antibiotic-resistant superbugs, it is essential to develop new compounds that can work against them. Our new compound was able to disrupt the cell membrane and kill the bacteria even at very low concentration of 5 microgram/mL,” says Dr. Jayanta Haldar, scientist at JNCASR and corresponding author of the paper.
Though the molecule alone was not able to disrupt biofilm, a combination of the molecule with erythromycin in equal concentration caused complete eradication of the tough-to-kill E. coli and Acinetobacter biofilm. Erythromycin by itself was also not able to disturb the biofilm. This showed that the combined strategy worked efficiently compared with individual antibiotics.
Double advantage
A combination of existing antibiotics (erythromycin) and the macromolecules also showed efficacy in treating burn and surgical wound infections caused by multi-drug resistant pathogens — Acinetobacter and Klebsiella — in animal models.
Conventional antibiotics were ineffective in the treatment of these infections in mice. However, the combination of macromolecules and the antibiotics could almost completely eradicate the burn and surgical wound infections and facilitate faster regeneration of the epithelial cells and hair follicles in mice models.
Collectively, these findings show the potential implications of the combination approach for topical treatment of infections. However, detailed animal studies are required further to fully understand the prospects of the molecule.
