Kenichiro Miyagawa

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.

Trehalose Accumulation by a Basidiomycotinous Yeast, Filobasidium floriforme

Abstract Screening was performed to isolate microorganisms which accumulate trehalose. Of 96 yeast strains screened, a basidiomycotinous yeast, Filobasidium floriforme IFO 1916, accumulated the largest amount of trehalose. Under optimum conditions in a 5- l jar fermentor, F. floriforme IFO 1916 accumulated 10 mg/ml trehalose (dry cell weight, 52 mg/ml; trehalose content, 20.0%) from 100 mg/ml glucose after cultivation for 24 h. Strain T12, a morphological and trehalose non-assimilating mutant of F. floriforme IFO 1916, accumulated 30% more trehalose than the parent strain.

Effect of Aspartic Acid Family Amino Acids on Production of Maridomycin III

An attempt was made to increase the production of maridomycin III (MDM III) as the major component among the six components of maridomycin (maridomycin I, II, III, IV, V and VI). Addition to the production medium, of amino acids belonging to the aspartic acid family and its related compounds, such as l-isoleucine, l-threonine, l-methionine, l-homoserine, dl-α-amino-n-butyric acid and α-ketobutyric acid, resulted in a yield of a large amount of MDM III.MDM III was also formed by intact cells from 4″-depropionyl MDM III and the same compounds. From 4″-depropionyl MDM III and l-isoleucine-U-14C (or dl-α-amino-n-butyric acid-3-14C), MDM III-14C was formed, and a large amount of radioactivity was incorporated into MDM III. On deacylation at C-4″ of the MDM III-14C, about 90% of radioactivity of MDM III-14C was observed as propionic acid-14CIn the same way, SF-837-14C was formed from leucomycin A7 and l-isoleucine-U-14C (or dl-α-amino-n-butyric acid-3-14C), and deacylation of the SF-837-14C at C–3 also gave pro...