Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae. I: Fermentation, isolation and biological properties

Abstract

The in vivo-mimic assay system using silkworm larvae was used as a screening tool to discover antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). Microbial culture broths were screened in this in vivo-mimic assay system and a culture broth of Streptomyces sp. K04-0144 was selected. New antibiotics, designated nosokomycins A-D, were isolated from the culture broth by HP-20 and ODS column chromatography and HPLC. Nosokomycins inhibited the growth of MRSA with MIC values of 0.125 microg ml(-1) using the liquid microdilution method. Furthermore, MRSA-infected silkworms survived when nosokomycin A or B was injected at a dose of 50 microg per larva.