| Abstract |
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.
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