Investigations into the Mechanism of Action of Sublancin

Antimicrobial resistance is a global threat that poses a rising concern. One underlying challenge is the limited number of targets in bacteria affected by the current pool of antibiotics. To potentially help find new targets, we studied a member of the class of antimicrobial natural products named glycocins. We examined the mode of action of sublancin, which contains an unusual and essential glucosylated Cys residue, by monitoring macromolecular synthesis. Sublancin negatively affected DNA replication, transcription, and translation without affecting cell wall biosynthesis. In addition, we confirmed that the presence of the PTS sugar glucose in the medium negatively impacted antimicrobial activity of sublancin. Additionally, sublancin analogues carrying different sugars retained their antimicrobial activity regardless of which sugar was attached to the peptide or the carbon source used. These data suggest a novel mechanism upstream of transcription and translation and are consistent with previous studies suggesting that the glucose uptake system is involved.