Micrococcins from Peribacillus sp. KDM594; efficacy against vancomycin-resistant enterococci and drug metabolism in a...

The screening of antibiotics derived from microbial resources to combat vancomycin-resistant enterococci (VRE) revealed that a culture of marine-derived Peribacillus sp. KDM594 exhibited significant therapeutic efficacy in an infected in vivo-mimic silkworm model. Bioassay-guided purification led to the isolation of micrococcins P1 (1) and P2 (2), which exhibited potent antimicrobial activities against Gram-positive bacteria, including VRE, methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium spp., with MIC values ranging from 0.25 to 8.0 µg ml^-1 using the microdilution method. In the silkworm models infected with VRE or MRSA, 1 and 2 exerted moderate therapeutic effects, with ED₅₀ values ranging from 3.2 to 51 µg larva^-1 g^-1. Furthermore, a pharmacokinetic analysis revealed that 2 was metabolized to 1 in the silkworm hemolymph, and their elimination half-lives were 3.2 and 3.0 h, respectively. These results suggest that micrococcins are promising lead compounds for the development of anti-VRE and MRSA drugs.