Work

Unique Features of Alarmone Metabolism in Clostridioides difficile

Year: 2022

Type: article

Abstract: Despite the role of the stringent response in antibiotic survival and recurrent infections, it has been a challenging target for antibacterial therapies because it is so ubiquitous. This is an especially relevant consideration for the treatment of Clostridioides difficile infection (CDI), as exposure to broad-spectrum antibiotics that harm commensal microbes is a major risk factor for CDI. Here, we report that both of the alarmone synthetase enzymes that mediate the stringent response in this organism employ a unique mechanism that requires the hydrolysis of two phosphate bonds and synthesize the triphosphate alarmone pGpp exclusively. Inhibitors targeted against these noncanonical synthetases have the potential to be highly specific and minimize detrimental effects to stringent response pathways in commensal microbes.

Source: Journal of Bacteriology

DOI: 10.1128/jb.00575-21