[Studies on uptake of macrolide antibiotics by Chlamydia host cell].

Minimum inhibitory concentration (MIC) of Macrolide antibiotic (ML) against C. trachomatis was found to greatly vary with the cell culture system used for the assay. We then investigated the ability of various cell cultures to uptake MLs in the relation to MIC determination. Penetration of the 14C-labeled MLs, Erythromycin, Jasamycin and Rokitamycin into cells was quantitatively studied by measuring the radioactivity incorporated into McCoy, HeLa229W and HeLa229F cells. It was found that HeLa229W cell showed the lowest MIC for the drugs, followed by HeLa229F cell and then by McCoy cell. Reversely, McCoy cell showed the lowest intracellular concentration of an ML, followed by HeLa229F cell and then by HeLa229W cell. These results indicate that MIC of an ML significantly varies depending on the ability of the test cell to uptake the drug.

19-Deformyl-4'-deoxydesmycosin (TMC-016): synthesis and biological properties of a unique 16-membered macrolide antibiotic.

19-Deformyl-4'-deoxydesmycosin was synthesized by the following synthetic route: 19-Deformylation of desmycosin, 3,2',4''-tri-O-trimethylsilylation, 4'-O-sulfonylation, 4'-iodination, reductive deiodination and 3,2',4''-tri-O-detrimethylsilylation. Deformylation of the aldehyde group at the C-19 position was achieved by two different methods: A) A simple one-step deformylation using Wilkinson's catalyst ((Ph3P)3RhCl). B) Reductive decarboxylation of the 19-carboxyl derivative following NaClO2 oxidation of the aldehyde. 19-Deformyl-4'-deoxydesmycosin showed very strong antimicrobial activity in vitro and in vivo.

[Synergistic activity of isepamicin and beta-lactam antibiotics against Pseudomonas aeruginosa in vitro and in vivo].

Synergistic activities of isepamicin (ISP) and a beta-lactam antibiotic such as piperacillin (PIPC) or cefotaxime (CTX) against Pseudomonas aeruginosa were demonstrated in vitro and in vivo. In vitro synergistic activity was observed when ISP was used together PIPC or CTX. The synergy observed in vitro was reproduced in vivo against experimental mouse infections, and a ISP-PIPC or a ISP-CTX combination showed significantly greater protective effects than individual antibiotics by themselves.

Taurocyamine-utilizing mutants from a wild-type strain of Pseudomonas.

Pseudomonas sp. ATCC 14676 produces glycocyaminase (EC 3.5.3.2) and guanidinobutyrase (EC 3.5.3.7). Taurocyamine (2-guanidinoethane sulfonate) is a gratuitous inducer of both of these amidinohydrolases. Mutants of this organism capable of utilizing taurocyamine as a nitrogen source were isolated directly from the wild-type cells after uv irradiation or treatment with N-methyl-N'-nitro-N-nitrosoguanidine; frequencies of mutations observed under appropriate conditions were above 10(-7). Strain U2-3-3, which was selected from the 11 isolated taurocyamine-utilizing strains, was proved to be derived from the wild-type strain. Both taurocyamine and 4-guanidinobutyrate were able to induce an enzyme of strain U2-3-3 that liberated urea from taurocyamine, whereas glycocyamine failed to induce the system. The activity of the enzyme toward taurocyamine was found to be about one-third of that toward guanidinobutyrate when both taurocyamine and guanidinobutyrate were used as inducer. These observations suggest that the enzyme of the mutant capable of hydrolyzing taurocyamine has emerged from guanidinobutyrase of the wild-type strain which hydrolyzes taurocyamine at a very low rate, probably as a result of a point mutation in the structural gene.