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PubMed1982

[Review [new antibiotics series III]: micronomicin (author's transl)].

Micronomicin is a new aminoglycosidic antibiotic discovered and developed by Kyowa Hakko Kogyo Co., Ltd. It is produced by Micromonospora sagamiensis var. nonreducans. Investigation of micronomicin performed in 134 research facilities in Japan led to the following results. 1) Micronomicin showed a broad antibacterial spectrum against Gram positive and Gram negative bacteria. 2) In susceptibility tests of clinical isolates, micronomicin was almost similarly active to GM. 3) Bactericidal activity of micronomicin against Pseudomonas aeruginosa and E. coli was higher than those of TOB and DKB. 4) Micronomicin showed a synergistic antibacterial activity against Pseudomonas aeruginosa and E. coli with CBPC and SBPC. 5) The therapeutic activity of micronomicin in mice infected with Pseudomonas aeruginosa and Serratia sp. was in high correlation with in vitro antibacterial activity similarly to that of GM. 6) Micronomicin was confirmed to be stable against aminoglycoside 6'-acetyltransferase of Pseudomonas aeruginosa and to be not inactivated. 7) Pharmacokinetics of micronomicin was almost similar to those of GM with respect to the concentrations in the serum, urine and tissues. 8) Ototoxicity of micronomicin in guinea pigs was found to be approximately four times less than that of GM. 9) Nephrotoxicity of micronomicin in rabbits was estimated to be less than those of GM and DKB. In rats, nephrotoxicity of micronomicin was approximately 4 times less than that of GM. 10) Micronomicin was effective on 964 cases out of 1,469 cases from 127 research facilities in Japan (65.6%), suggesting its favorable activity against respiratory tract infections and against urinary tract infections. 11) Side effects with the drug were observed in 43 cases out of 1,532 cases (2.81%). Abnormalities in laboratory findings were also recognized, but transient without severe cases. 12) In conclusion, micronomicin is a favorable drug having lesser ototoxicity and nephrotoxicity as well as antibacterial and bactericidal activity of aminoglycosidic antibiotics usually used.

Aminoglycosides↗
PubMed1997

[Determination of the nucleotide sequence of the silent aminoglycoside phosphotransferase gene in Streptomyces rimosus P3].

The nucleotide sequence BgIII-Pstl of the DNA fragment containing the aph gene cloned from Streptomyces rimosus P3 not producing aminoglycoside antibiotics was determined. The aph gene was shown to encode neomycin phosphotransferase differing by the substrate specificity from the enzyme encoded by the aph genes from the organisms producing aminoglycoside antibiotics. Comparison of the cloned aph VIII gene and its product with the aph genes and their products from the antibiotic-producing actinomycetes and clinical microbial strains permitted to consider it as a representative of the third group genes which are likely widely distributed in soil microorganisms not producing aminoglycoside antibiotics. The gene length was 777 nucleotide pairs at the average GC content of 67 per cent. Comparison of the nucleotide and protein sequences of the S.rimosus gene with those of the genes cloned from the aminoglycoside-producing organisms (S.fradiae and Micromonospora chalcea) revealed high homology in the 3'-end region of the genes. However, the homology percentage by DNA for the S.rimosus gene was lower than that for the genes from the other organisms on their comparison with each other: 56-67 and 82-86 per cent respectively. Comparison of the profiles of the protein hydrophilic properties revealed differences in the region of the first 110 amino acids of the gene under the investigation. The amino acid sequence contained all the highly conservative regions characteristics of aminoglycoside phosphotransferases but had several amino acid substitutes detected for the first time including those in the region responsible for the antibiotic binding.

Amino Acid Sequence↗
PubMedDate not supplied

[Use of electrical impulses for selective isolation of actinomycetes f rom soil].

A new method was elaborated for the selective isolation of actinomycetes from soil, which involves the pretreatment of soil samples with electric pulses. The treatment of soil with 3-ms electric pulses at a field intensity of 12 kV/cm2 resulted in a significant (threefold on average) increase in the proportion of representatives of rare actinomycetes isolated. This treatment regime was found to be most efficient for the selective isolation of representatives of the genera Actinoplanes, Micromonospora, Actinomadura, and Microtetraspora. The proportion of representatives of the genera Streptosporangium and Saccharotrix also increased. The treatment of soil samples with 3-ms electric pulses at a field intensity of 16 kV/cm resulted in highly selective isolation of representatives of the genus Nocardioides.

Actinomycetales↗
PubMed2000

High-resolution LC/MS for analysis of minor components in complex mixtures: negative ion ESI for identification of impurities and degradation products of a novel oligosaccharide antibiotic.

High-resolution mass spectrometry has been routinely used for structural confirmation and identification; however, it has mostly been applied to relatively pure samples. Exact mass measurement of minor components such as impurities, degradation products or metabolites in complex mixtures has been difficult without prior separation and isolation. Here we report the utilization of on-line liquid chromatography in combination with high-resolution mass spectrometry for the identification of impurities and base degradation products of Sch 27899, a member of the everninomicin class of antibiotics. Nine Sch 27899-related impurities and degradation products were detected by negative ion electrospray ionization using a magnetic sector mass spectrometer. Exact mass measurements were obtained at a resolution of 5000 using polyethylene glycol (PEG) sulfates as internal standards. Corresponding elemental compositions were determined within a 2 ppm error tolerance and structures were proposed for all components.

Aminoglycosides↗
PubMed2004

Antifungal activity of actinomycetes from Cuban soils.

This study reports on the capacity of actinomycete strains isolated from Cuban soils to produce antifungal agents. The antimicrobial activities were determined by susceptibility disk assay methods. We isolated 563 different actinomycetes and 286 produced compounds with antifungal activity. Our screening method indicated the presence of many possible polyene macrolide antibiotics and the important antifungal activity in the soils rich in minerals.

Actinobacteria↗