coumermycin and Disease-Models--Animal

Burkholderia pseudomallei causes melioidosis, a potentially lethal disease that can establish both chronic and acute infections in humans. It is inherently recalcitrant to many antibiotics, there is a paucity of effective treatment options and there is no vaccine. In the present study, the efficacies of selected aminocoumarin compounds, DNA gyrase inhibitors that were discovered in the 1950s but are not in clinical use for the treatment of melioidosis were investigated. Clorobiocin and coumermycin were shown to be particularly effective in treating B. pseudomallei infection in vivo. A novel formulation with dl-tryptophan or l-tyrosine was shown to further enhance aminocoumarin potency in vivo. It was demonstrated that coumermycin has superior pharmacokinetic properties compared with novobiocin, and the coumermycin in l-tyrosine formulation can be used as an effective treatment for acute respiratory melioidosis in a murine model. Repurposing of existing approved antibiotics offers new resources in a challenging era of drug development and antimicrobial resistance.

Topics: Aminocoumarins; Animals; Burkholderia pseudomallei; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Melioidosis; Mice; Mice, Inbred BALB C; Moths; Novobiocin; Tryptophan

Herpes simplex virus type 1 was reactivated from the trigeminal ganglia of latently infected mice in a quantitative and time-dependent manner. Novobiocin and coumermycin A1 reversibly inhibited the reactivation of herpes simplex virus type 1. They did not inhibit viral replication in permissive cells (CV-1) but did inhibit replication in cells of neuronal origin (C1300) and acutely infected trigeminal ganglia.

Topics: Aminocoumarins; Animals; Anti-Bacterial Agents; Cell Line; Coumarins; Disease Models, Animal; Herpes Simplex; Mice; Novobiocin; Recurrence; Simplexvirus; Trigeminal Ganglion; Trigeminal Nerve; Virus Replication