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Biomedical subjects

S Mitsuhashi

Publications and source records attributed to S Mitsuhashi.

At least 325 records · Page 18Linked to original sources
PubMed1975

R factor-mediated aminoglycoside antibiotic resistance in Pseudomonas aeruginosa: a new aminoglycoside 6'-N-acetyltransferase.

The newly introduced semisynthetic aminoglycoside antibiotics, i.e., 3',4'-dideoxykanamycin B (DKB), 6'-N-methyl DKB (6'-Me-DKB) and amikacin (AK) have been found to be effective against gram-negative pathogens including Pseudomonas aeruginosa, which are resistant to the known aminoglycoside antibiotics. We have demonstrated in our stock cultures two types of P. aeruginosa strains resistant to DKB, i.e., (DKB(r).AK(r).6'-Me-DKB(s)) and (DKB(r).AK(s).6'-Me-DKB(r)) (where r = resistant; s = sensitive). Both groups of strains inactivate the drugs by acetylation. The acetylating enzyme was extracted from GN4925(DKB(r).AK(s).6'-Me-DKB(r)) and purified by affinity chromatography. Enzymatic studies of the inactivation reaction and chemical studies of the inactivated products indicated that DKB and 6'-Me-DKB were inactivated by acetylation of the 6'-amino group of the drugs. This enzyme acetylates kanamycin A (KM-A), KM-B, DKB, 6'-Me-DKB, 6'-N-methyl kanamycin B, but not KM-C, AK, and gentamicin C(1). The enzyme is named aminoglycoside 6'-N-acetyltransferase 3. Genetic studies of two strains resistant to DKB and 6'-Me-DKB disclosed that the enzyme catalyzing inactivation of both DKB and 6'-Me-DKB was mediated by an R factor, i.e., R(ms167) and R(ms168), capable of conferring resistance to KM, DKB, and 6'-Me-DKB, in addition to resistance to gentamicin, streptomycin, and sulfanilamide, and resistance to tetracycline, chloramphenicol, streptomycin and sulfanilamide respectively.

Acetyltransferases↗
PubMed1975

Artificial elimination of drug resistance from group A beta-hemolytic streptococci.

Ten strains of beta-hemolytic streptococci were tested for elimination of resistance to macrolide antibiotics, tetracycline, and chloramphenicol. Six of the strains lost resistance after cultivation at 41 C or addition of acriflavine (0.2 mug/ml). These results suggest that determinants governing resistance to these antibiotics are located on extrachromosomal genetic elements (plasmids) that are widely distributed in streptococci.

Acriflavine↗
PubMed1975

Biochemical properties of a penicillin beta-lactamase mediated by R factor from Bordetella bronchiseptica.

The beta-lactamase specified by an R(te16) plasmid in Bordetella bronchiseptica was purified 200-fold by carboxymethyl-Sephadex column chromatography and electrofocusing. The enzyme has a molecular weight of 46,000 +/- 3,000 and an isoelectric point of 8.3 and was highly active against phenethicillin, oxacillin, and propicillin. The enzyme activity was inhibited by sodium chloride but not by ferrous ion. The maximal enzyme activity to benzylpenicillin was observed at pH 7.0 to 7.5 and at 40 C. It is concluded that this enzyme is different from the R-mediated beta-lactamases, i.e., the type I and type II beta-lactamases which have been classified in previous papers.

Bacterial Proteins↗
PubMed1975

Gentic properties of an R factor carrying resistance to aminolgycoside antibiotics.

R factor Rms 151 is an fi+ R factor and belongs to a incompatibility group FII. It carries the genes governing resistance to various aminoglycoside antibiotics, i.e., kanamycin (KM), lividomycin (LV), gentamicin C complex (GM), and 3',4'-dideoxykanamycin B (DKB), in addition to those governing to tetracycline (TC), chloramphenicol (CM), sulfanilamide (SA), and ampicillin (APC). Electron microscopy observation disclosed that the Rms151 deoxyribonucleic acid was a circular form with length of 31.2 mum. A probable circular genetic map of Rms151 was proposed by genetic and biochemical studies, the genes being in the order of -tet-tra-amp-aad-sul-aph-cml-, in which aad and aph confer resistance to KM.GM.DKB by adenylytransferase or resistance to KM.LV by phosphotransferase, respectively.

Aminoglycosides↗
PubMed1974

Relationship between chloramphenicol acetyltransferase activity and the number of resistance genes.

Various mutants of an Escherichia coli K-12 strain were prepared, in which a chloramphenicol (CM) resistance gene (cml) derived from an R factor, R100-1, was integrated into the chromosome. The CM acetyltransferase (CATase) activity of these strains and the strain carrying R100-1 were determined during exponential growth with the following results. (i) The CATase activity varied, depending upon the site of integration of the cml gene on the chromosome. Activity was found to be higher when the cml gene was integrated nearer the replication origin of the chromosome, the total enzyme activity found was the sum of activities coded by each gene separately. (iii) When the cml gene was in a cytoplasmic state on an R factor, R100-1, the expressed enzyme activity was four-to eightfold higher than that in the chromosomal state, suggesting the existence of about four to eight copies of R factor per chromosome. The CATase activity returned to the level of that expressed by R100-1 when the chromosomal cml gene was detached and picked up by an R factor.

Acetyltransferases↗
PubMed1974

Demonstration of R factors from Pseudomonas aeruginosa.

Sixty strains of Pseudomonas aeruginosa were selected from our clinical stock cultures and used as donors of drug resistance to examine the presence of R factors. They were highly resistant to one or more of six drugs including tetracycline (TC), chloramphenicol (CM), streptomycin (SM), sulfanilamide (SA), carbenicillin (CPC), and kanamycin (KM). Three FP(-), auxotrophic mutants of P. aeruginosa were used as recipients, which had been made resistant to either rifampin (RMP) or KM by in vitro mutation. Each donor was mated with each of the three recipients, and 45 strains were found to transfer their resistance to one or more recipients. A second series of conjugation experiments using 45 exconjugants as donors showed that 23 could transfer their resistance. We conclude that these strains carry R factors that are transmissible to one or more recipients. Eleven carried resistance to (TC.CM.SM.SA.CPC), nine to (TC.CM.SM.SA), one to (TC.CM.SA.CPC), one to (TC.CM.SA), and one to (SM). All of these R factors could not be transmitted to other species belonging to the family Enterobacteriaceae.

Anti-Bacterial Agents↗
PubMed1974

Enzymatic inactivation of a new aminoglycoside antibiotic, sisomicin by resistant strains of Pseudomonas aeruginosa.

The antibacterial activity of sisomicin (SS), a new aminoglycoside antibiotic active toward clinical isolates of Pseudomonas aeruginosa, was determined and compared with that of the gentamicin C complex. Both drugs were effective against these strains and showed almost the same antibacterial activity. A few strains were found to be resistant to SS. The antibiotic was inactivated by a cell-free extract from the SS-resistant strains due to acetylation of the drug. Comparative studies of the inactivation of the drugs which lack a 6'-amino group in the amino sugar linked to 2-deoxystreptamine strongly suggested that SS inactivation was due to acetylation of the 6'-amino group of the 4',5'-didehydropurpurosamine moiety.

Acetylation↗
PubMed1974

Properties of R factors from Bordetella bronchiseptica.

Genetic properties and host ranges of R factors derived from Bordetella bronchiseptica of pig origin were examined. All of 61 R factors tested could confer resistance to streptomycin, sulfonamide, and aminobenzyl penicillin on their host bacteria. All of them were identified as fi(-) (no fertility inhibition) type and were found to exhibit no restriction of phages lambda, phi80, P1, P2, T1, T3, T6, T7, W31, and BF-23. They could confer macarbomysin susceptibility on their host cells when infected. An Rte16, a representative R factor, was incompatible with both RP4 and R40a, which are classified as compatibility groups P and C, respectively. An Rte16 was conjugally transmissible to B. bronchiseptica, Escherichia coli, Citrobacter freundii, Salmonella typhimurium, and Yersinia enterocolitica, but not to Shigella flexneri, S. sonnei, Proteus mirabilis, P. vulgaris, P. rettgeri, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Anti-Bacterial Agents↗
PubMed1974

R-factor mutant capable of specifying hypersynthesis of penicillinase.

The physical characteristics of a mutant, R(M201-2), capable of conferring high and stable ampicillion resistance was analyzed. The R(M201-2) and its parent R-factor deoxyribonucleic acid (DNA) could be isolated as an extrachromosomal and covalently closed circular form. Their buoyant densities were both 1.712 g/cm(3), and their molecular weights were about 82 x 10(6) and 64 x 10(6), respectively, when measured by CsCl and sucrose density gradient analyses. The contour lengths by electron microscopy were 35.9 +/- 0.6 and 31.0 +/- 0.6 mum, respectively. By using the extracted R-factor DNA, the mutant and parent characters were transformable to another Escherichia coli strain. The mutant R factor showed an increased amount of DNA even after conjugal transfer to Proteus. An increase in the size of R-factor DNA was thus considered to be the cause of the high level of ampicillin resistance.

Ampicillin↗