EM49, a novel peptide antibiotic produced by Bacillus circulans, shows broad-spectrum antibacterial activity in vitro and also has substantial activity against yeasts, fungi, and protozoa. Its high degree of antipseudomonal activity and its greater activity against gram-negative than against gram-positive bacteria are noteworthy. EM49 is rapidly biocidal to populations of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. Even after ten successive subcultures in the presence of EM49, strains of P. aeruginosa, E. coli and S. aureus did not develop any resistance to this compound. The antibiotic was active in vivo upon subcutaneous administration to mice infected with Streptococcus pyogenes C203 or E. coli, but was inactive when given by the oral route. Whenapplied topically at a concentration of 0.5 %in a cream base, EM49prevented the multiplication of P. aeruginosa in experimentally induced wounds in mice.The discovery of a new, broad-spectrum, peptide antibiotic produced by Bacillus circulans ATCC21,656 has been reported1*. The antibiotic is a mixture of octapeptides, presumably cyclic, that are acylated with a C10 or Cn fatty acid side chain2). Though closely related to the polymyxin group of antibiotics, EM49is distinguished from the polymyxins by a difference in the number of amino acid residues, by a lack of threonine, and by differences in the nature of the fatty acid moieties with respect to the numberof carbon atoms and the presence of a /3-hydroxy group2). The lack of cross-resistance between EM49and polymyxin B, and the greater antistaphylococcal activity of EM49, also serve to differentiate these compounds10. In this manuscript, we describe our studies on the behavior of this antibiotic in vitro and in vivo and on the taxonomic characterization of the producing organism, Bacillus circulans ATCC21,656.
ExperimentalAll minimal inhibitory concentration values (MIC) described in this report were determined by a standard, twofold broth-dilution technique.The minimal biocidal concentration (MBC), was determined by subculturing all tubes from the MIC titrations without visible growth onto antibioticfree agar medium. The subculture end points were read after 48 hours of incubation at 37°C, and the MBCwas defined as the lowest concentration of antibiotic that did not allow growth of the organism on subculture.Evaluation of the efficacy of EM49was done in groups of CD-I (Charles River) male mice, 16~18 g, that were infected experimentally. Evaluation in the Streptococcus pyogenes C203 model infection was as previously described by Miraglia and Basch3). The experimental Escherichia coli infection was produced by the intraperitoneal injection of a suitably diluted culture of E. coli Squibb Culture (SC) 8294, so that each mouse received 100 LD50 doses suspended in 1 ml of 5 % hog gastric mucin. Treatment was given as a single dose within 1 hour after infection. The medicaments, in 5%gumacacia or in water, were administered by subcutaneous injection or by gavage. All
