Anovel antibiotic, GE2270A, was isolated from the fermentation broth of a strain of Planobispora rosea. The product was found to inhibit bacterial protein synthesis. Structural characteristics showed similarities between GE2270 A and thiazolyl peptides such as micrococcin which is known to inhibit protein synthesis by acting directly on the ribosome. Despite this similarity GE2270A showed functional analogy to kirromycin-like antibiotics and pulvomycin, as its molecular target was found to be elongation factor Tu (EF-Tu). GE2270A is active against Gram-positive microorganism and anaerobes and differs from the other EF-Tu inhibitors in its spectrum of antimicrobial activity. 693 GE2270A, a novel peptide antibiotic, emerged from a screening program designed to detect inhibitors of protein synthesis. The present paper deals with the discovery, isolation, initial physico-chemical and biological characterization of this antibiotic. Materials and Methods Cultural and Growth Characteristics of the Producing Strain Colonial and morphological characters were determined with standard methods1'2*. Color determination was madeaccording to Maerz and Paul3). Growthon sole sources of carbon was determined after incubation at 28°C for 2 weeks1*. Chemotaxonomic Characteristics of the Producing Strain Freeze-dried biomass was examined to determine the major chemotaxonomiccharacteristics. Cell wall diamino acids were determined by TLCby a modification of the method of Becker et a/.4)5). Wholecell sugars were hydrolyzed, reduced and derivatized. The resultant alditol acetates were analyzed by GC6). Fatty acid methyl esters were similarly analyzed by GC7). Menaquinones and polar lipids were extracted and analyzed by HPLCand 2D TLC, respectively8*. Fermentation of the Producing Strain A 500-ml Erlenmeyer flask containing 100 ml of seed medium (Pdlypeptone 0.5%, yeast extract 0.3%, beef extract 0.2%, soybean meal 0.2%, starch 2%, calcium carbonate 1%, pH 7.0) was inoculated from an oatmeal slant of the producing strain. After incubation at 28°C for 96 hours on a rotary shaker (200 rpm), the biomass was transferred to a 10-liter jar fermenter containing 4 liters of the seed medium. This culture was grown for 72 hours at 28°C with 2 liters/minute air flow and stirring at 900rpm, prior to inoculating a jar fermenter containing 50 liters of production medium(starch 2%, peptone 0.25%,

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In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Neisseria gonorrhoeae. A40926 was rapidly bactericidal for N. gonorrhoeae clinical isolates at concentrations equal to or slightly higher than the MIC. In mice, levels in serum were higher and more prolonged than those of an equivalent subcutaneous dose of teicoplanin. These properties suggest that A40926 may have potential in the therapy of gonorrhea.The increased frequency of isolation of multiply antibioticresistant gram-positive bacteria has led to wider use of antibacterial agents which were originally rarely considered for first-line therapy, such as the glycopeptide vancomycin (18). One of the advantages of this antibiotic is that, thus far, resistance is rare and restricted to certain coagulase-negative staphylococci (25). The success of vancomycin has stimulated the development of new glycopeptides, such as teicoplanin (5,13,32,33). These antibiotics inhibit cell wall biosynthesis by binding to the D-alanyl-D-alanine portion of nascent peptidoglycan (22). Specific binding to an affinity resin containing acyl-D-alanyl-D-alanine groups (9) formed the basis of our search for new glycopeptides.Among the new glycopeptides identified, we focused our attention on those having novel biological properties. A40926 is the most interesting antibiotic which has emerged thus far from our screening campaign. In fermentation broths, we found it as a complex of four factors (PA, PB, A, and B). PA and PB, described here for the first time, predominated in the broth; during purification, these two compounds were largely converted to A and B, whose structures have been described recently (31a). One feature of all four factors, which relates them to teicoplanin and some other glycopeptides (aridicins and kibdellins) (3, 27, 12) while distinguishing them from vancomycin, ristocetin, and others, is the presence of a fatty acid moiety attached to one of the sugars. In terms of biological activity, the most striking difference between the components of the A40926 complex and other glycopeptide antibiotics is their activity against Neisseria gonorrhoeae.MATERIALS AND METHODS Isolation of A40926. We screened specifically for glycopeptide antibiotics by passing fermentation broths over the affinity resin Sepharose-D-alanyl-D-alanine (9) and eluting adsorbed glycopeptides with 1% aqueous ammonia. The strain producing A40926 was found in a soil sample collected in India. Batch adsorption to the same affinity resin described above yielded nearly pure A40926 complex in one step. Quick neutralization of the ammonia eluate yielded primarily the two fac...

Teichomycin, a new glycopeptide antibiotic with a spectrum of activity similar to that of vancomycin, was highly active against staphylococci, streptococci and Gram-positive anaerobes (Propionibacterium acnes, Clostridium perfringens and Cl. difficile). Ninety per cent of the Staphylococcus aureus and streptococcal strains, including enterococci, were inhibited by 0.4 mg/l; 90% of Staph. epidermidis strains were susceptible to 1.6 mg/l. Vancomycin was less active than teichomycin against all clinical isolates tested. Multiply resistant strains, including methicillin-resistant Staph. aureus, were all susceptible to teichomycin and vancomycin. Teichomycin was highly bactericidal for growing cells of staphylococci and Streptococcus pyogenes and moderately bactericidal for Str. faecalis. In mice, teichomycin was well absorbed upon subcutaneous administration and had a half-life of 2.5 h. It was very effective in curing experimental mouse septicemias caused by Gram-positive bacteria (ED50 values less than 1 mg/kg).

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