This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Worldwide, antibiotic resistance is associated with millions of deaths every year, and the World Health Organization warns that the number of resistant infections is rising. Colistin is a last-resort antibiotic used when other treatments fail, but rates of colistin-resistant infections are rising as well, putting people at even greater risk and increasing the urgency for new therapeutic approaches.
Recent findings from lab and animal studies point to a promising way to resensitize pathogens to the antibiotic. In Microbiology Spectrum, researchers in China report that combining colistin with L-arginine, an amino acid, restored sensitivity to the drug in bacteria with colistin resistance genes. The combination changes the cell membrane, allowing colistin to move inside.
This influx triggers the intracellular production of reactive oxygen species, which kill the bacterium. In experiments on mice, the combination effectively treated infections by colistin-resistant pathogens. "This dual-targeted approach represents a rational strategy to overcome colistin resistance," said senior author Guo-Bao Tian, Ph.D., a microbiologist at Sun Yat-sen University's Zhongshan School of Medicine.
Colistin was first approved in 1959 for use in life-threatening infections caused by gram-negative bacteria, but was widely avoided due to high toxicity and severe side effects. The emergence of superbugs, pathogenic bacteria resistant to potent antibiotics, in the 1990s led to increased use of the drug as a last-resort therapeutic. Complicating matters, genes that confer colistin resistance spread via small circular bits of DNA called plasmids that bacteria easily share.
In recent years, researchers have probed diverse strategies for resensitizing bacteria to colistin, combining the antibiotic with nanomaterials or other drugs, for example. Metabolites, which are produced by the body during metabolism, show some antibiotic activity and have been studied as potential boosters because of how they remodel interactions between the pathogens and the antibiotic. Amino acids, however, have received less attention, said Tian.
Tian and his collaborators focused on L-arginine, an amino acid that in previous studies has been shown to enhance the efficacy of an antibiotic in resistant infections. They found that the combination effectively and quickly killed strains of Escherichia coli with the mcr-1 gene, which drives resistance in colistin-resistant microbes. L-arginine and colistin, when administered alone, showed minimal antibacterial activity.
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