Teicoplanin, a new antibiotic from Actinoplanes teichomyceticus nov. sp

Abstract

Teicoplanin, a new glycopeptide antibiotic belonging to the same family as vancomycin, inhibits cell wall synthesis in Bacillus subtilis; the inhibition is accompanied by an intracellular accumulation of UDP-N-acetylmuramyl-pentapetide. A cell-free system from Bacillus stearothermophilus, capable of synthesizing peptidoglycan, is 50% inhibited by teicoplanin at 40 ,ug/ml and 100,% inhibited at 100 ,ug/ml; suppression of peptidoglycan synthesis is accompanied by parallel accumulation of the lipid intermediate. Teicoplanin binds to cell walls and forms a complex with N,N'-diacetyl-L-lysyl-D-alanyl-D-alanine. The association constant of this complex is 2.56 X 106 liters mol'1, calculated by spectrophotometric titration. The mechanism of action of teicoplanin is discussed in comparison with those of other inhibitors of cell wall biosynthesis, namely, vancomycin, ristocetin, and gardimycin.Teicoplanin is a new antibiotic chemically related to the group of glycopeptides which also includes vancomycin and ristocetin. It was isolated from the fermentation broth of Actinoplanes teichomyceticus nov. sp. (1, 12) and is endowed with outstanding bactericidal activity against grampositive pathogenic bacteria (11). The antibiotic is a mixture of five components of very similar polarity (the T-A2 complex, formerly named teichomycin A2) and a more polar product (T-A3); the components of the T-A2 complex, accounting for 90 to 95% of the product, have the same molecular weight, ca. 1,900 (2).The main features distinguishing teicoplanin from the other glycopeptide antibiotics are the occurrence of glucosamine as the basic sugar and the presence of aliphatic acid residues. Teicoplanin is not active against the L form of Staphylococcus aureus derived from a susceptible strain (12); this is a primary indication that the antibiotic interacts with the bacterial cell wall. We made further investigations on the mechanism of action of teicoplanin, and we present data showing that: (i) teicoplanin inhibits peptidoglycan synthesis in intact cells and in "cell-free" systems; (ii) the inhibition by teicoplanin is reverted by cell wall; (iii) the antibiotic binds to walls of whole cells, rendering them resistant to the action of lysozyme; and (iv) a complex occurs between teicoplanin and the peptide N,N'-diacetyl-L-lysyl-D-alanyl-D-alanine (Ac2-L-lys-D-ala-D-ala), a synthetic analog of the pentapeptide precursor in the peptidoglycan synthesis.Part of this work was presented at the 12th International Congress of Chemotherapy, July 1981, Florence, Italy. MATERIALS AND METHODSBacterial strains and growth conditions. Bacillus subtilis SB25 (His-Try-) and PB556/1 (Thy-), derived from strain W168, were grown in Difco Penassay medium (PY) or in Davis minimal medium (4) with the appropriate supplements in flasks at 37°C with reciprocating shaking. Bacillus stearothermophilus (calidolactis) ATCC 10149 was grown at 55°C in 4-liter tanks with forced aeration in a medium containing Incorporation of radioactive macromolecule precursors. B. subtilis 556/1 wa...

Actinoplanes lichenis sp. nov., isolated from lichen

“…At the time of writing, the genus Actinoplanes comprises 39 species with validly published names (Parte, 2014). Some antibiotics have been shown to be produced by strains of species of Actinoplanes such as lipiarmycin (anti Gram-positive bacteria activity), teicoplanin (inhibits cell wall synthesis of Gram-positive bacteria) and friulimicin (has peptidoglycan synthesis inhibiting activity) from Actinoplanes deccanensis, Actinoplanes teichomyceticus and Actinoplanes friuliensis, respectively (Aretz et al, 2000;Coronelli et al, 1975;Somma et al, 1984).We have attempted to find a novel source, other than terrestrial soils, for isolating novel actinomycetes. Recent studies have described the isolation of different species of actinomycete from lichen, such as Actinomycetospora iriomotensis (Yamamura et al, 2011a), Actinomycetospora rishiriensis (Yamamura et al, 2011b) and Nocardioides exalbidus (Li et al, 2007).…”

“…At the time of writing, the genus Actinoplanes comprises 39 species with validly published names (Parte, 2014). Some antibiotics have been shown to be produced by strains of species of Actinoplanes such as lipiarmycin (anti Gram-positive bacteria activity), teicoplanin (inhibits cell wall synthesis of Gram-positive bacteria) and friulimicin (has peptidoglycan synthesis inhibiting activity) from Actinoplanes deccanensis, Actinoplanes teichomyceticus and Actinoplanes friuliensis, respectively (Aretz et al, 2000;Coronelli et al, 1975;Somma et al, 1984).…”

Bacteriolytic effect of teicoplanin

“…A consequence of the binding of teicoplanin to the bacterial cell wall (Somma et al, 1984) is that simple washing of cells pretreated with the antibiotic is not sufficient to prevent lysis. B. pumilus CCM 1697 pretreated with 2 pg teicoplanin ml-1 for 15 min, washed and transferred to fresh medium or buffers behaved as if the antibiotic was still present (Fig.…”

Determination of teicoplanin concentrations in serum by high-pressure liquid chromatography

“…3:50-51, 1984). It appears to inhibit cell wall biosynthesis in gram-positive organisms by interfering with peptidoglycan polymerization (12). Pharmacokinetic investigations showed a multiexponential concentration in blood-versus-time profile with elimination halflives of 45 to 50 h (13), which is 6 to 10 times longer than that of vancomycin.…”