Tsuneo Kanamaru

In Vitro and In Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of Helicobacter pylori Infection

ABSTRACT The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 μg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure ofH. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

Emeriamine, an antidiabetic β-aminobetaine derived from a novel fungal metabolite

Abstract Emeriamine [(R)-3-amino-4-trimethylaminobutyric acid], derived from a novel fungal metabolite “emericedin” [(R)-3-acetylamino-4-trimethylaminobutyric acid], was proved to be a strong and specific inhibitor of carnitine-dependent oxidation of long chain fatty acid (IC 50 ; 3.2 × 10 −6 M) and its main inhibition site was shown to be carnitine palmitoyltransferase I located on the outer-surface of the mitochondrial inner membrane. Emeriamine also showed hypoglycemic and antiketogenic activities in a dose-dependent manner (1–10 mg/kg) when administered orally to fasted normal and diabetic animals.

Actinocorallia gen. nov., a new genus of the order Actinomycetales

One species of the new genus Actinocorallia, Actinocorallia herbida sp. nov., is described. The genus Actinocorallia is characterized by well-developed, branched, nonfragmented substrate mycelia. On the tips of unique coralloid sporophores, which arise from the substrate mycelia, long chains of nonmotile spores (more than 30 spores per chain) are borne. On rare occasions formation of coremia is observed. The chemotaxonomic characteristics of this organism are as follows: the cell wall chemotype is type III (meso-diaminopimelic acid), the whole-cell sugar pattern is type C (no diagnostic sugar type), the fatty acid pattern is type 1a (straight-chain saturated acids and monounsaturated acids), the predominant isoprenoid quinones are MK-9(H4) and MK-9(H6), phospholipid type PII (phosphatidylethanolamine) is present as the diagnostic polar lipid, the N-acyl type of muramic acid in the cell wall is the acetyl type, and the guanine-plus-cytosine content of the DNA is 73 mol%. The type strain of A. herbida is strain AL-50780 (= IFO 15485).

Separation and Identification of UDP-N-Acetylhexosamine Derivatives Excreted by Penicillin-treated Corynebacterium alkanolyticum

N-Acetylhexosamine derivatives, which are intermediates of cell wall synthesis, were detected in UV-absorbing substances excreted by penicillin-treated Corynebacterium alkanolyticum. Gel filtration, using Sephadex G-25, separated N-acetylhexosamine derivatives to three components, each of which was purified by Dowex 1 × 2 column and paper chromatographies.From the analytical studies, N-acetylhexosamine derivatives were found to be composed of UDP-N-acetylmuramic acid-(diaminopimelic acid, glutamic acid, alanine), UDP-N-acetylhexosaminuronic acid and UDP-N-acetylglucosamine.