Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties.

An antifungal activity against Mucor hiemalis was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce90. The activity was excreted into the supernatant during the log and early stationary phase. When the adsorber resin XAD-16 was added to the culture, the active metabolites were quantitatively bound to the resin. The epothilons showed a high cytotoxicity for animal cells and mimic the biological effects of taxol (BOLLAG et al., Cancer Res. 55: 2325 approximately 2333, 1995).

The jerangolids: A family of new antifungal compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties of jerangolid A.

An antifungal activity was detected in the culture broth of the myxobacterium, Sorangium cellulosum strain So ce 307. The activity was excreted into the supernatant during the log and early stationary phase. When the organism was fermented in the presence of the adsorber resin XAD-16, the metabolite was quantitatively bound to the resin. The main component, jerangolid A, has structural similarities to ambruticin, which is also produced by strains of Sorangium cellulosum.

Chivosazol A, a new inhibitor of eukaryotic organisms isolated from myxobacteria.

A new antibiotic, chivosazol, was isolated from the culture broth of the myxobacterium Sorangium cellulosum strain So ce12. It is a macrocyclic ring with one oxazol ring and a glycosidically bound 6-deoxyglucose (quinovose) at C-11. The antibiotic shows antimicrobial activity against yeasts and filamentous fungi, and is especially potent against mammalian cells. It was not active against bacteria.

Ratjadon: a new antifungal compound from Sorangium cellulosum (myxobacteria) production, physio-chemical and biological properties.

An antifungal activity, ratjadon, was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce360. The metabolite was quantitatively bound to the adsorber resin XAD-16, which was added to the medium at the beginning of the fermentation. The antibiotic spectrum was narrow, but some important phytopathogenic fungi, especially species of Oomycetes, were inhibited at very low concentrations.

The ripostatins, novel inhibitors of eubacterial RNA polymerase isolated from myxobacteria.

A new antibiotic, ripostatin, was isolated from the culture supernatant of the myxobacterium, sorangium cellulosum strain So ce377. It is a macrocyclic lactone carbonic acid containing an unsubstituted phenyl ring in a side chain. The antibiotic acts especially on Staphylococcus aureus, but seems not to penetrate most bacteria. The MIC values are in the range of 1 microgram/ml. Ripostatin is an inhibitor of eubacterial RNA polymerase. It interferes with the initiation of RNA synthesis.

The tartrolons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum.

New antibiotics were isolated from the culture broth of the myxobacterium, Sorangium cellulosum, strain So ce 678. The antibiotics were active against Gram-positive bacteria and mammalian cells. They were named tartrolon A and B. Tartrolon B contains a boron atom. The boron binding region of tartrolon is identical with that of boromycin and aplasmomycin.

Disorazol A, an efficient inhibitor of eukaryotic organisms isolated from myxobacteria.

A new antibiotic, disorazol, was isolated from the culture broth of the myxobacterium, Sorangium cellulosum strain So ce 12. It is a macrocyclic compound containing two oxazole rings. The antibiotic acted against many fungi and mammalian cell cultures. The latter responded to extremely low doses (MIC 3-30 pg/ml). None of the tested bacteria and yeasts were inhibited.

The soraphens: a family of novel antifungal compounds from Sorangium cellulosum (Myxobacteria). I. Soraphen A1 alpha: fermentation, isolation, biological properties.

An antifungal activity was detected in the culture broth of Sorangium cellulosum (Myxococcales), strain So ce26. The activity was excreted into the supernatant during the log and early stationary phase. The active substance was quantitatively bound to XAD absorber resin added to the medium at the beginning of the fermentation. The new secondary metabolite was called soraphen and is of special interest to plant disease control for its inhibitory activity against numerous phytopathogenic fungi.

Saframycin Mx1, a new natural saframycin isolated from a myxobacterium.

A new natural saframycin was discovered in the culture broth of the myxobacterium, Myxococcus xanthus strain Mx x48. The fermentation and isolation of the antibiotic are described. The name, saframycin Mx1, is proposed. The compound appears to interact with cellular DNA.

The sorangicins, novel and powerful inhibitors of eubacterial RNA polymerase isolated from myxobacteria.

A new antibiotic, sorangicin, was isolated from the culture supernatant of the myxobacterium, Sorangium (Polyangium) cellulosum strain So cel2. It is a macrocyclic lactone carbonic acid and is produced in two structural variants, sorangicins A and B. In addition small quantities of the respective glycosides, sorangiosids A and B, may be found. The antibiotic acts mainly against Gram-positive bacteria, including myocobacteria, with MIC values between 0.01 and 0.1 microgram/ml, but at higher concentrations (MIC 3 approximately 30 micrograms/ml) Gram-negatives are also inhibited. Yeasts and molds are completely resistant. The new antibiotic is a specific inhibitor of eubacterial RNA polymerase which it blocks, however, only if added before RNA polymerization has started.

A new algorithm for individual dialysis prescription based on urea kinetics.

Methods for calculating required dialysis time to maintain certain blood urea nitrogen levels predialytically thus far have neglected the influence of ultrafiltration during hemodialysis and of weight changes in the interdialytic period. We therefore have developed a new algorithm for individual dialysis prescription based on urea kinetics which further optimizes accuracy of dialysis prescription by considering these two factors. The accuracy of this new method was proven in a prospective follow-up of 3 patients during some 9 consecutive hemodialysis session. It was found that there was a very close relation between the measured and the predicted values of blood urea nitrogen, the difference being only due to variations in dietary protein intake as the patients were kept on liberal food intake. The new algorithm is easily implemented into a pocket calculator and thus can be used under arbitrary dialysis conditions.

[Individual dialysis using computer-controlled prescription]. / Individuelle Dialyse durch computergesteuerte Vorschreibung.

The use of urea kinetics as basis for optimization and individualization of renal replacement therapy has become quite popular over the last decade. The rationale underlying the use of blood urea nitrogen for monitoring or targeting dialysis therapy is based on the report of an American multicentre cooperative dialysis study showing that blood urea nitrogen concentrations are closely correlated to the occurrence of morbidity and complications in dialysis patients. In order to further optimize the accuracy of dialysis prescription we have developed a new algorithm for estimation of the dialysis time needed to reach a certain blood urea nitrogen concentration, which--in contrast to all methods employed so far--enables accurate calculation of ultrafiltration during haemodialysis and of weight changes in the interdialytic period.

The mechanism of action of myxovalargin A, a peptide antibiotic from Myxococcus fulvus.

Myxovalargin A has two modes of action. At low concentrations (below 1 microgram/ml) it inhibits bacterial protein synthesis specifically and instantaneously. In vitro experiments suggest that it interferes with the binding of aminoacyl tRNA to the A site of the ribosome. At higher concentrations (above 5 micrograms/ml), or upon prolonged incubation, the antibiotic damages cell membranes. This leads to secondary effects, like decreased O2 consumption or instant break down of RNA synthesis, and may be the reason for the irreversibility of the antibiotic action. The membrane effect is not restricted to prokaryotes and may explain the high toxicity of the compound for higher organisms.

The corallopyronins, new inhibitors of bacterial RNA synthesis from Myxobacteria.

From the culture broth of the myxobacterium, Corallococcus (Myxococcus) coralloides, three new antibiotics have been isolated: corallopyronin A, B and C. The compounds, which are chemically related to the recently discovered myxopyronins, act mainly on Gram-positive bacteria, with MIC values between 0.1 and 10 micrograms/ml, and only exceptionally or at much higher concentrations (MIC values; 100 and more micrograms/ml) on Gram-negatives. They do not inhibit eukaryotic organisms and show no toxicity for mice (sc). The corallopyronins appear to block specifically eubacterial RNA polymerase.

Iron removal by desferrioxamine in patients on chronic hemodialysis--kinetic study and long-term results.

Serum ferritin levels, cumulative number of administered blood transfusions, number of monthly transfused blood units and total months on hemodialysis (HD) treatment differed significantly in 7 patients on hemodialysis with clinical, biochemical and histological evidence of hemosiderosis, when compared to 37 controls (p less than 0.001 for all parameters). As a new treatment method desferrioxamine (DFO) therapy was introduced for iron detoxification in these hemosiderotic chronically hemodialyzed patients. Hence, to maximize the biological half-time, 30 mg/kg body weight DFO were given after the end of HD in the iron-loaded patients. Iron removal during the subsequent HD and the increase of iron excretion by the stool after DFO was measured by atomic absorption spectroscopy. Iron removal by the artificial kidney was calculated by investigating the function (QDi + QF)CDo over the duration of HD treatment, which equals the total amount of iron removal during HD. Using numerical integration of measured data this removal was found to be 21.8 +/- 6.9 mg whereas cumulative iron loss via the feces was found to be 36.5 +/- 14.6 mg. Therefore, total iron elimination was calculated to be on average 50-60 mg after administration of a single dose of DFO. Furthermore, long-term treatment of 5 patients resulted in a significant decrease of serum ferritin levels from 2,309 +/- 295 to 715 +/- 177 ng WHO/ml (p less than 0.001) after a period of 36 +/- 5 months. We conclude, that DFO in a dosage of 30 mg/kg body weight given at the end of HD is able to remove more than 500 mg iron/month if it is administered following each HD. Long-term results indicate negative iron balance without significant change of transfusion frequency if not more than 2 U of blood (500 mg iron) are administered within 1 month. This treatment schedule might be superior compared to the previously used methods of administration where DFO was given at the beginning or throughout HD.

The myxopyronins, new inhibitors of bacterial RNA synthesis from Myxococcus fulvus (Myxobacterales).

From the culture supernatant of the myxobacterium, Myxococcus fulvus strain Mx f50, an antibiotic activity was isolated which blocked growth of many Gram-positive and several Gram-negative bacteria, but not of yeasts and fungi. The activity consisted of two closely related compounds, myxopyronins A and B. The myxopyronins appear to be new antibiotics, and seem to specifically inhibit bacterial RNA polymerase.