Therapeutic Efficacy and Drug Metabolism of Griseorhodin A Induced by a Co-culture of Actinomycete Strain TMPU-20A002 and Mycobacterium smegmatis in Silkworm Infection Models.

In screening for antibacterial agents from co-cultures of Mycobacterium smegmatis and microbial resources, such as actinomycetes and fungi, the known hydroxyquinone antibiotic griseorhodin A (1) was isolated from a co-culture of actinomycete strain TMPU-20A002 and M. smegmatis. Compound 1 exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE), with minimum inhibitory concentrations of 0.25 and 2.0 μg/mL, respectively. In silkworm infection models with MRSA and VRE, 1 exhibited therapeutic efficacy, with ED50 values of 2.5 and 18 μg/larva·g, respectively. A pharmacokinetic analysis of silkworms revealed an elimination half-life of 4.4 h in the hemolymph, indicating a favorable metabolic profile. This is the first in vivo evaluation of griseorhodin A, including its pharmacological activity and metabolic behavior, and it highlights its potential as a candidate for the development of novel antibacterial agents.