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Biomedical subjects

H L David

Publications and source records attributed to H L David.

At least 109 records · Page 6Linked to original sources

Differential identification of Mycobacterium kansasii and Mycobacterium marinum.

This report deals with the differential diagnosis between Mycobacterium marinum and M. kansasii. We found that the two species could be differentiated by using six main tests, namely, the nitrate reduction test, the arylsulfatase test, the ability to grow in the presence of 10.0 mug of amithiazone per ml, the ability to grow in the presence of 5.0 mug of kanamycin per ml, the temperature-ratio test, and the rate of growth on solid medium. In contrast to M. kansasii, considerable variation was observed among strains of M. marinum. However, the evidence obtained was not considered sufficient to justify the conclusion that more than one species was represented among the strains identified as M. marinum.

Anti-Bacterial Agents↗

Resistance to D-cycloserine in the tubercle bacilli: mutation rate and transport of alanine in parental cells and drug-resistant mutants.

A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CS(r)/perm(+)) mutant and a d-cycloserine-resistant permease-defective (d-CS(r)/perm(-)) mutant were isolated. The d-CS(r)/perm(-) mutant was not found to be more resistant to the drug than was the d-CS(r)/perm(+) mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10(-10) mutations per bacterium per generation.

Alanine↗

Purified protoplasmic peptides of mycobacteria: chemical composition of a tuberculin-active glycopeptide.

A tuberculin-active glycopeptide containing eight different amino acids and glucose was isolated from the protoplasm of Mycobacterium tuberculosis. A molecular weight of 4,000 to 5,000 was established by Sephadex gel filtration; other analyses showed a peptide to carbohydrate ratio of 9:1. These observations suggest a tentative composition of 3 to 4 residues of glucose, 12 residues each of aspartic and glutamic acids, 3 residues each of lysine, glycine, and serine, and 1 residue each of arginine, threonine, and alanine.

Alanine↗

Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis.

The fluctuation test shows that Mycobacterium tuberculosis mutates to resistance to isoniazid, streptomycin, ethambutol and rifampin spontaneously and at random. The average mutation rates for the drugs, in the same order, were calculated to be 2.56 x 10(-8), 2.95 x 10(-8), 10(-7), and 2.25 x 10(-10) mutation per bacterium per generation. The relatively high mutation rate to ethambutol resistance and the low mutation rate to rifampin resistance were confirmed by analyzing the increase in the proportion of mutants with time in a growing population of the tubercle bacilli. The highest proportions of mutants to be expected in unselected populations of the tubercle bacilli were calculated from the results of fluctuation tests.

Culture Media↗

Inhibition of the Synthesis of Wax D Peptidoglycolipid of Mycobacterium tuberculosis by d-Cycloserine.

The antibiotic d-cycloserine inhibits the synthesis of the wax D peptidoglycolipid in cells of the H37Ra strain of Mycobacterium tuberculosis. This inhibition occurs at a lower concentration of the drug than that required for the inhibition of growth. The inhibition is completely reversed by d-alanine. An arabino-galactan-galactosamine-(diaminopimelic acid)-mycolate accumulates in H37Ra cells exposed to the antibiotic. The chemical and functional group analyses of this lipid suggests it to be a possible precursor to the synthesis of wax D.

Journal Article↗

Action of antituberculous and beta-lactam drugs (including imipenem) against extra- and intra-cellularly growing Mycobacterium avium-intracellulare.

The extracellular and intracellular activities of 4 antituberculous drugs (rifampicin, streptomycin, ansamycin and kanamycin) and 7 beta-lactam antibiotics (penicillin G, amoxycillin, carbenicillin, ticarcillin, ampicillin, cloxacillin and imipenem) were determined against the bacteria of the Mycobacterium avium complex (MAC). The extracellular activities were determined against 14 strains by the broth-dilution method, whereas the intracellular activities were determined against type strain ATCC 15769 multiplying actively inside murine J-774 macrophages. Six of the beta-lactam drugs (except the beta-lactamase-stable drug imipenem) were also used in association with the beta-lactamase inhibitor clavulanic acid. Our results showed that the screening of MAC strains against beta-lactams may be useful, and that correlation of usual in vitro minimal inhibitory concentrations with the intracellular activities of the same drugs against pathogenic mycobacteria, whenever feasible, would be the method of choice to designate the therapeutic protocols against these intracellular pathogens.

Animals↗