Barry Rosen, Ph.D.
Florida International University
NIEHS grantees demonstrated that a recently discovered natural product, called arsinothricin (AST), that contains arsenic and has broad-spectrum antibiotic activity. AST is produced by soil bacteria that live around the roots of rice plants. According to the authors, their findings suggest that this soil bacteria has evolved the ability to use arsenic, a toxic soil contaminant, to its advantage.
The researchers tested AST and found it to be effective against pathogens such as Escherichia coli, which can cause severe intestinal infections, and carbapenem-resistant Enterobacter cloacae, a common cause of infections in neonatal and intensive care units, and a World Health Organization global priority pathogen. It was also effective against Mycobacterium bovis, the causative agent of animal tuberculosis.
They found that resistance to AST arose with the prolonged use of the antibiotic and pinpointed that the gene arsN1 was responsible for producing an enzyme that conferred resistance to pathogens. According to the authors, it may be possible to develop arsN1 inhibitors, which block arsN1 activity, for use in combination with AST to prevent resistance.
Researchers tested AST toxicity on human blood cells and found that it had low cell toxicity and was much less toxic to human cells than a more common form of arsenic. According to the authors, these compounds have potential for future clinical use, but further testing is necessary to better determine effectiveness and toxicity.
Citation: Nadar VS, Chen J, Dheeman DS, Galvan AE, Yoshinaga-Sakurai K, Kandavelu P, Sankaran B, Kuramata M, Ishikawa S, Rosen BP, Yoshinaga M. 2019. Arsinothricin, an arsenic-containing non-proteinogenic amino acid analog of glutamate, is a broad-spectrum antibiotic. Commun Biol 2:131.