New Antibiotic Discovery from Soil Bacterium
Scientists have identified a potent antibiotic from a soil bacterium that could prove effective against drug-resistant infections. This insight came from studying how Streptomyces coelicolor naturally produces methylenomycin A, a drug known since 1965.
In research published on Monday in the Journal of the American Chemical Society, the team examined the intricate pathways the bacterium uses. They found an intermediate compound, premethylenomycin C lactone, which exhibited antimicrobial activity that was 100 times greater than that of methylenomycin A. Interestingly, incredibly tiny doses of this compound were able to eliminate strains of bacteria associated with challenging infections.
Study co-author Gregory Challis, a chemical biologist at the University of Warwick, described the finding as a surprise. He reflected on how people might assume that evolution perfects the final product, making it the most potent form. Yet, this discovery illustrates how evolution can sometimes take unexpected paths, which Challis refers to as a “blind watchmaker” approach.
The increasing threat of antimicrobial resistance is alarming, with projections suggesting it could lead to 39 million deaths globally over the next 25 years. Researchers are hopeful that this new antimicrobial compound could inspire the development of new medications.
Gerard Wright, a biochemist at McMaster University, emphasized the importance of this research in uncovering new bioactive compounds from established pathways.
Background of the Study
Challis and his team began exploring how Streptomyces coelicolor creates methylenomycin A back in 2006. They systematically deleted genes responsible for producing key enzymes in the process, building on previous genomic sequencing work done in 2002.
By 2010, the researchers had delineated the mechanism for creating methylenomycin A and identified several intermediate molecules produced during this process. “Initially, we were just conducting general exploratory research,” Challis noted, mentioning that they later put these intermediates aside as their functions were unclear.
It wasn’t until around 2017 that a graduate student in Challis’s lab decided to investigate the antimicrobial effectiveness of those intermediate molecules. Two compounds, including premethylenomycin C lactone, turned out to be significantly more effective than methylenomycin A against several strains of Gram-positive bacteria. These include Staphylococcus aureus, known for causing skin, blood, and internal organ infections, as well as Enterococcus faecium, associated with severe bloodstream and urinary infections.
Remarkably, only 1 microgram per milliliter of premethylenomycin C lactone was needed to eradicate drug-resistant strains of Staphylococcus aureus, a stark contrast to the 256 micrograms required of methylenomycin A. Moreover, it proved effective at much lower doses compared to vancomycin, a last-resort antibiotic for specific strains of Enterococcus faecium.
