With the aid of a small number of additional diagnostic criteria, antibiotic treatment for UTI can be provided more specifically and thus more effectively. Differentiating UTI from asymptomatic bacteriuria, which usually requires no treatment, can lower the frequency of unnecessary antibiotic prescriptions.
In the course of ongoing research efforts aimed at exploring the biosynthetical potential of freshly isolated actinomycetes, the secondary metabolite profile of streptomycete strain Tu 6075 was subjected to a closer scrutiny. HPLC-diode-array analysis (HPLC-DAD) coupled with HPLC-electrospray-mass-spectrometry (HPLC-ESI-MS) revealed a pattern of metabolites in the extracts from the culture filtrate and mycelium that could not be identified by means of our HPLC-UV-Vis-Database2). The database contains about 700 reference compounds, most of which are antibiotics. Two series of homologous metabolites with retention times between 9.0 and 11.4 minutes were produced by strain Tu 6075, having end-absorption in the UV range and a side-maximum at 290 and 295nm, respectively. The spectra showed a high conformity with reference compounds of the peptide sub-library stored in
Materials and Methods
MicroorganismsStrain Tu 6075 was isolated from a soil sample collected in the tropical rain forest at Cape Coast, Ghana, using yeast extract-malt extract agar with addition of cycloheximide (50mg/liter) and nalidixic acid (20mg/liter)4). The strain is deposited in the culture collection of our laboratory under
The structures of new lipopeptide antibiotics, arylomycins A and B, were elucidated by a combination of ESI-FTICR-mass spectrometry, NMR spectroscopy, EDMAN sequencing, and fatty acid and chiral amino acid analyses. The colourless arylomycins A share the peptide [3,3]biaryl bond between MeHpg5 and Tyr7. The yellow arylomycins B differ from arylomycins A by nitro substitution of Tyr7. The N-termini of arylomycins A and B are acylated with saturated C11-C15 fatty acids (fa1) comprising n, iso, and anteiso isomers. Arylomycins A and B represent the first examples of biaryl-bridged lipopeptides.Arylomycins were isolated from the fermentation broth of Streptomyces sp. Tu 6075 (Fig. 1). The taxonomy of the producing organism, fermentation, isolation, and biological activities of arylomycins are described in the preceding paper1). Here, we present the structure elucidation of these novel compounds.
A detailed screening of the secondary metabolite pattern produced by different athropod associated strains of the species Streptomyces anulatus resulted in the isolation and structure elucidation of the endophenazines A-D (2, 4-6). The structures were assigned by spectroscopic methods and chemical transformations. 4 represents a chromophoric system based on a phenazin-7-one, 5 and 6 are new 5,10-dihydrophenazine derivatives.In the course of our screening for bioactive compounds from endosymbiontic microorganisms we investigated athropod associated microorganisms by analyzing their metabolite pattern. The extracts of Streptomyces anulatus (strains 9663, 9843, 9958 and 10099) were applied to our chemical screening programme2). HPTLC analysis resulted in five substances utilising their colour, UV absorption and colourization by Ehrlich's reagent. The substances were identified as phenazine derivatives.In the previous paper the taxonomy of Streptomyces anulatus as well as the fermentation, isolation and biological activities of the endophenazines have been described1). In this part we present the structure elucidation of these antibiotics mainly done by NMR analysis.
Structure ElucidationPhenazine-1-carboxylic acid (1), isolated from the culture filtrate of the strain 9663, was identified by comparison of its spectroscopic data with the data given in the literature3,4). The UV spectrum of endophenazine A (2) is very similar to that of 1, indicating a further phenazine derivative. The 1H NMR spectrum shows six aromatic protons, their coupling pattern points to a 1,6-or 1,9-disubstituted phenazine skeleton. From the molecular formula (C13H8N2O2) and the data obtained from the NMR spectra a carboxyl and a C5-prenyl group can be derived as substituents. Due to a NOE between the acidic proton of the carboxyl and the methine group of the prenyl residue, the regiochemistry of the substituents was unambiguously
BAL30376 is a triple combination comprising a siderophore monobactam, BAL19764; a novel bridged monobactam, BAL29880, which specifically inhibits class C -lactamases; and clavulanic acid, which inhibits many class A and some class D -lactamases. The MIC 90 was <4 g/ml (expressed as the concentration of BAL19764) for most species of the Enterobacteriaceae family, including strains that produced metallo--lactamases and were resistant to all of the other -lactams tested. The MIC 90 for Stenotrophomonas maltophilia was 2 g/ml, for multidrug-resistant (MDR) Pseudomonas aeruginosa it was 8 g/ml, and for MDR Acinetobacter and Burkholderia spp. it was 16 g/ml. The presence of the class C -lactamase inhibitor BAL29880 contributed significantly to the activity of BAL30376 against strains of Citrobacter freundii, Enterobacter species, Serratia marcescens, and P. aeruginosa. The presence of clavulanic acid contributed significantly to the activity against many strains of Escherichia coli and Klebsiella pneumoniae that produced class A extended-spectrum -lactamases. The activity of BAL30376 against strains with metallo--lactamases was largely attributable to the intrinsic stability of the monobactam BAL19764 toward these enzymes. Considering its three components, BAL30376 was unexpectedly refractory toward the development of stable resistance.
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