A novel series of milbemycin antibiotics were produced by soil isolate, strain E225 which was shownto be a Streptomycesspecies. The antibiotics displayed anthelmintic activity against Trichostrongylus colubriformis in the gerbil. Twoof the compounds, VM44857 and VM44866 were shownto be potent anthelmintics against mixed nematodeinfections in sheep.The milbemycins are a large family of closely related macrolide antibiotics produced by species of the genus Streptomyces. The first reported members of the family, milbemycins, ax to a10 and pt to /?3 were isolated from Streptomyces hygroscopicus subsp. aureolacrimosus as a result of an insecticidal screening programme1}. Subsequent communications described further members of the series from the original strain2), or its mutants3'40. Biological properties of these milbemycins have not been extensively reported but the anthelmintic activity of milbemycin D against dog parasites has been published5). A further series of milbemycins with anthelmintic activity was described from Streptomyces cyaneogriseus subsp.
noncyanogenus6) and Streptomyces thermoarchaensis7'8).Milbemycins were also isolated from a hybrid microorganism obtained by protoplast fusion of Streptomyces avermitilis and S. hygroscopicus9).This paper describes a novel series of milbemycin anthelmintics isolated from a new strain of the genus Strep tomyces.
Materials and MethodsIn Vitro Anthelmintic Test A suspension of the infective larval stage (L3) of Haemonchuscontortus was prepared by culturing faeces from experimentally infected sheep. The suspension was cleaned and concentrated by the standard Baermanntechnique. Samplesfor anthelmintic testing, whether purified compoundsor microbial culture extracts were prepared in methanol solution. Samples (0.1 ml) were evaporated to dryness in microtitre plates and L3 suspension (0.1 ml) was added. After incubation at 4°C overnight the plates were warmed to room temperature and larval motility was assessed visually in comparison to controls. For purified compoundsMICvalues were defined as the minimumconcentration which caused approximately 75%of the wormsto show reduction in motility.
An amylopectinlike polysaccharide (granulose) was the only glucan produced in significant quantities by six wild-type strains of Clostridium pasteurianum grown in glucose minimal medium. The intracellular polysaccharide granules laid down before sporulation contained only this amylopectin. No intracellular dextran was discovered in these wild-type strains, nor in a granulose-negative mutant strain of C. pasteurianum possessing an ADP glucose pyrophosphorylase (EC2.7.7.27) but lacking a granulose synthase (i.e. ADP glucose-alpha-1,4-glucan glucosyl transferase, EC2.4.1.21). Furthermore, methylation analysis demonstrated that (1 leads to 6) linked alpha-D-glucose units accounted for less than 2% of the entire glucose content of these organisms.
The skin is a habitat for microbes that commonly infect preterm infants, but the use of sequencing for fine-scale study of the microbial communities of skin that develop in these infants has been limited by technical barriers. We treated skin swabs of preterm infants with a photoreactive dye that eliminates DNA from nonviable microbes and then sequenced the remaining DNA.
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