NAI-107 [Microbisporicin]

Isolated from Microbispora sp. White to off-white powder. Soluble in DMSO, aqueous acetonitrile or ethanol. Antibacterial class I lantibiotic. Mixture of two similarly active and structurally related polypeptides (A1, 2246Da and A2, 2230Da) of 24 amino acids linked by 5 intramolecular thioether bridges. Inhibits cell wall synthesis and consequently bacterial growth by forming a complex with lipid intermediate II (Lipid II), a key intermediate in peptidoglycan biosynthesis. Efficiently interfers with late stages of cell wall biosynthesis leading to accumulation of the soluble peptidoglycan precursor UDP-N-acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Active against aerobic and anaerobic Gram-positive pathogens, including all antibiotic-resistant strains (e.g. MRSA and VRE) in whole cell and in vitro assays as well as in vivo. Rapidly bactericidal and highly efficacious in experimental models of infection (septicemia, endocarditis, granuloma pouch) and developed for treatment of serious infections by multiresistant Gram-positive bacteria.