Search PubMed⌕ Search

Biomedical subjects

J T Smith

Publications and source records attributed to J T Smith.

At least 199 records · Page 11Linked to original sources
PubMed1974

Trimethoprim action and its analogy with thymine starvation.

In a minimal medium, trimethoprim is merely bacteriostatic on the prototroph Escherichia coli 114. The drug was bactericidal when the amino acids methionine and glycine, plus a purine or purine nucleoside, were also present. This response could be reversed completely when thymine and lysine were added to the culture. Methionine, glycine, and the purine are thought to maintain the integrity of the tetrahydrofolate pool under trimethoprim treatment and prevent the thymidylate synthetase reaction. Thus, the organism behaves phenotypically as a thymineless mutant. The mechanisms by which thymine and lysine reverse the bactericidal effect of trimethoprim in a minimal medium containing methionine, glycine, and adenine is discussed.

Chloramphenicol↗
PubMed1974

Ampicillin resistance of Shigella sonnei.

The ampicillin resistance of clinical isolates of Shigella sonnei is due to beta-lactamase production. Two kinds of resistance are found: low level, nontransmissible; and high level, tranmissible. The nontransmissible type of resistance results from a chromosomal mutation which increases the production of a beta-lactamase that hydrolyses cephalosporins relatively rapidly and gives cephalothin resistance. The transmissible type of resistance is due to an R factor mediating the synthesis of a different beta-lactamase that does not significantly hydrolyze cephalosporins or confer cephalothin resistance. One clinical isolate is shown to possess simultaneously both these mechanisms of ampicillin resistance.

Ampicillin Resistance↗
PubMed1974

Molecular specificities of R factor-determined beta-lactamases: correlation with plasmid compatibility.

Beta (beta)-lactamases determined by 29 ampicillin resistance plasmids could be divided into two types. One, TEM-type, was very uniform with respect to substrate specificity but heterogeneous in absolute levels of beta-lactamase activity. The TEM-type beta-lactamase was determined by R factors of compatibility groups FII, Ialpha, Iepsilon, N, C, A, T, W, P, L, and X, and by prophage phi Amp. The other type, characterized by the ability to hydrolyze oxacillin, was less common, showed lower absolute levels of activity, and was heterogeneous as regards substrate specificities. Oxacillin-hydrolyzing beta-lactamases were determined by R factors of compatibility groups FI, Ialpha, N, C, and O.

Ampicillin↗
PubMed1974

Relation of R factor and chromosomal beta-lactamase with the periplasmic space.

The release of several R factor and chromosomal beta-lactamases by osmotic shock treatment was studied. It was found that those beta-lactamases with a molecular weight of about 20,000 were released, but those with a molecular weight of about 30,000 to 44,000 were not released during osmotic shock. This differential release did not depend on whether the structural genes were on the chromosome or on the genome of an R factor. The release or retention of the beta-lactamases appeared to be a characteristic of the enzyme rather than the host cell since the same results were obtained when the R factors were harbored by a variety of host bacteria. Studies with bacteria which produced more than one beta-lactamase showed that each enzyme reacted independently to the presence of other beta-lactamases produced by the host bacterium.

Anti-Bacterial Agents↗
PubMed1974

R-factor-mediated nuclease activity involved in thymineless elimination.

R-factor 1818 (R-1818) had no effect on the efficiency of plating of ligase-deficient phage T4 mutants on strains of Escherichia coli containing excess, normal, or defective ligase. However, if the R(+) bacterial strain that overproduced ligase was first starved of thymine, its ability to propagate ligase-deficient phage was reduced by as much as fivefold compared with the burst size on the thymine-starved R(-) strain. In contrast, it was found that after ultraviolet irradiation of the host the phage burst size was higher on the R(+) ligase overproducing strain than the R(-) derivative. The maximal level of R-factor elimination produced by thymine starvation was inversely related to the ligase level of the host. Ultraviolet irradiation did not cure the R factor from strains containing wild-type levels of ligase, but did cause elimination from strains with excess or defective ligase. The results suggest that R-1818 codes for a nuclease that is induced by thymine starvation and which, possibly in conjunction with host-mediated nucleases, is responsible for its elimination under these conditions.

Anti-Bacterial Agents↗
PubMed1974

R-factor-mediated beta-lactamases that hydrolyze oxacillin: evidence for two distinct groups.

The enzymatic and molecular properties of 14 oxacillin-hydrolyzing beta-lactamases, all of them R-factor-specified, were studied, and two distinct groups were found. Four of the enzymes had a molecular weight of 24,000, were active against methicillin, and had an electrophoretic mobility of -0.1 cm/h. Eight enzymes had a molecular weight of 45,000, low activity against methicillin, and an electrophoretic mobility of +0.5 cm/h. The remaining two enzymes were similar to those of the second group in being relatively inactive against methicillin, but their molecular weight was lower (42,000) and their electrophoretic mobility was different (-0.1 cm/h). All the enzymes of both groups were sensitive to inhibition by sodium chloride. The two groups were not completely homogeneous in their enzymatic properties; seven possible subtypes could be recognized.

Ampicillin↗
PubMed1973

Curing of an R factor Escherichia coli by trimethoprim.

R factor 1818, which we have shown previously to be eliminated by thymine starvation, was cured from three strains of Escherichia coli K-12 by overnight exposure to trimethoprim. Elimination was abolished in the presence of added thymine or thymidine, which suggests that curing is the result of the induction of thymineless conditions by trimethoprim. Starvation of the required amino acids proline and histidine had little effect on elimination, whereas methionine deprivation enhanced it. R factor curing was abolished by the presence of chloramphenicol, and it is concluded that protein synthesis is required for elimination to occur. It is suggested that elimination may result from the activity of a nuclease which is synthesized or induced during both direct thymine starvation and by trimethoprim treatment.

Amino Acids↗