France: In this world of increasing frequency of antibiotic resistance, that renders antibiotics ineffective, there arises a need for antibiotic alternatives that do not trigger resistance. In a bid to search for the same, a team of French researchers have developed a novel class of antibiotics that were effective against gram-positive and negative multi-resistant bacteria. Most importantly, the new antibiotics did not trigger resistance or cause toxicity while they were experimented to cause toxicity in mice. The antibiotic is based on a natural bacterial toxin.
The study is published in the journal PLOS Biology.
Antibiotics are medical wonders but their overuse has led to the development of antibiotic resistance and emergence of superbugs. According to WHO, antibiotic resistance is the biggest threats to human health globally and is expedited by antibiotic misuse in both humans and animals.
The team led by Brice Felden, Director of the Bacterial Regulatory RNAs and Medicine laboratory in Rennes, synthesized and designed the compounds called peptidomimetics, by imitating a section of a toxin produced by S aureus to kill other bacteria (PepA). In a test against a broad spectrum of gram-negative and gram-positive pathogens, Pep16 and Pep19 were found to be effective against methicillin-resistant S aureus (MRSA) and Pseudomonas aeruginosa in mouse models. The number of deaths from MRSA is increasing each year and by the year 2050, it is estimated that at least 10 million people will die annually as a result of antimicrobial resistance.
Testing of the compounds on human erythrocytes and kidney cells, zebrafish embryos, and mice showed no toxicity. In addition, after 2 weeks of serial passage performed against multidrug-resistant clinical isolates in vitro, and 4 or 6 days exposure in mice infected with MRSA, the compounds showed no development of resistance.
Analysis of the mechanism of action indicates the compounds are able to permeate the cell membranes of gram-positive and gram-negative bacteria, leading to bacterial death.
“We have identified potential therapeutic agents that can provide alternative treatments against antimicrobial resistance. Because the compounds are potential leads for therapeutic development, the next step is to start phase I clinical trials,” concluded the authors.
To read the complete study follow the link: https://doi.org/10.1371/journal.pbio.3000337