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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

The expression of mammalian drug metabolising enzymes in S. cerevisiae

Black, S. M. 1990 (has links)
Adaptation to a chemically challenging environment is a critical aspect of the evolutionary process. As a result a wide variety of systems involved in xenobiotic metabolism have evolved. Two such systems are the phase I (drug toxification) Cytochrome P-450 monooxygenases and the phase II (drug detoxification) glutathione S-transferases. In order to evaluate the role of specific gene products in chemical toxicity and mutagenicity members of each of these groups have been expressed in the lower eukaryote S.cerevisiae and the mutation frequency and sensitivity to a wide variety of cytotoxic agents examined. A cDNA encoding the rat P-450IIB1 protein has been expressed to a level of between 0.1-0.2% of total yeast protein. The protein was localised to the microsomal fraction and found to be functional as determined by activity towards the model substrate, benzyloxyresorufin. An attempt was made to develop this P450IIB1 expressing strain as a viable short term test (STT) for the screening of potential mutagens. To this end the strain was exposed to a series of known mutagens all requiring metabolic activation by cytochrome P-450 to exert their effects. An increase in mutation frequency, as determined by resistance to L-canavanine, was obtained when exposed to the anticancer drug, cyclophosphamide and the mycotoxin, sterigmatocystin. The PB-inducible cytochrome P-450's have been implicated in the metabolism of these chemicals. The specificity and potential of this P450IIB1 expressing strain and the possibilities for the expression of cytochrome P-450's in S.cerevisiae as an STT is discussed. The overexpression of the glutathione S-transferases (GST) has been associated with the drug resistance. In order to directly evaluate this possibility the human alpha (B1B1) and pi class GST have been expressed in S.cerevisiae either singly or in tandem. These strains were then exposed to a variety of alkylating agents, anticancer drugs and organic hydroperoxides to determine if GST overexpression modulates sensitivity to cytotoxic insult. In all cases GST expression resulted in a significant reduction in the cytotoxic effects of these agents. These data provide evidence that the overexpression of GST observed in cells resistant to anticancer drugs is directly involved in the resistance mechanism.
2

Investigation of mesophilic Aeromonas : response to hydrogen peroxide and role in false-positive Colilert reaction

Landre, Julien B. P. 1999 (has links)
Mesophilic Aeromonas are opportunistic human pathogens which produce a wide range of virulence factors and have been isolated from both untreated and chlorinated drinking waters. The presence of these microorganisms in the distribution systems suggests that Aeromonas could display an adaptive response to oxidant present during water treatment. This adaptive response of Aeromonas would lead to interference in analysis for faecal coliforms used to determine the quality of potable drinking water, and be a potential source of intestinal disorders. The Colilert defmed substrate technology system was developed as a one-step detection of both coliforms and E. coli while suppressing non-coliform heterotrophic growth. Aeromonas species were previously shown to cause production of falsepositive reaction at high cell densities (Edberg et ai., 1988). Similar results were obtained in our study when using fresh Colilert reagents. However, results obtained during this project showed Aeromonas to mediate false-positive reactions at low cell densities (101 cells/ml in presence of salt, 102 cells/ml in absence of salt) when using Colilert reagents within 4 weeks prior to shelf-life expiry. Increased incidence in falsepositive reactions mediated by Aeromonas were shown to be dependent upon the stability of the Colilert reagent affected with age. Such Aeromonas interference would lead to over-estimation of coliforms and E. coli in potable drinking water supplies. The ability of bacteria to adapt to a wide range of stress factors such as pH, heat shock, oxidants or starvation has been extensively studied. Little is known about the response of Aeromonas to such stress conditions. During this project, it has been demonstrated that mesophilic Aeromonas display an adaptive tolerance response to a lethal oxidative challenge through pre-treatment with a sub-lethal dose of oxidant. The stress adaptation process was demonstrated to occur through synthesis of stress proteins and modulation of pre-existing catalase. Of the species studied, A. sobria was most sensitive, whereas A. caviae and A. hydrophila displayed similar responses to oxidative stress. The hypersensitivity of A. sobria did not impair the adaptive response of the organism. During our investigations, stationary phase Aeromonas cells have been shown to be more resistant than their logarithmic counterpart and suggested that excreted molecules may playa role in protecting the cells. Re-suspension of fresh cells into spent medium from a stationary phase cells revealed a higher resistance of these cells compared to those re-suspended in minimal medium. This resistance was demonstrated to be mediated by non-proteinaceous, thermo-sensitive effector molecule. A potential candidate as the effector molecule, butyryl homo serine lactone, was synthesised and assayed. Preliminary data strongly suggest that this molecule has a role to play in the stress adaptation phenomenon and might be involved in stimulating synthesis of key stress proteins.
3

A novel selection method for Salmonella

Druggan, Patrick 2007 (has links)
In 1967 the International Standards Organisation drew up a method designed to resuscitate a single injured Salmonella cell in 25 g of food. This method takes five days and introduced a pre-enrichment step that allowed injured Salmonella species to recover their resistance to selective agents before they were inoculated in to selective medium. Since 1967 a variety of methods has been developed that shorten the time .taken to detect a positive sample, yet these methods rely on the pre-enrichment step to allow injured Salmonella cells to recover and to allow amplification. This work was carried out to improve recovery ofinjured cells and allow selection during the pre-enrichment phase. Using variants of Buffered Peptone Water as recovery media, it was found that heatinjured Salmonella cells comprised a number of distinct sub-populations, based on their ability to recover in different broths. It was found that anoxic conditions improved recovery of heat-injured cells, while media that allowed rapid growth inhibited recovery. A survey of commercially available BPW found a> 2 10gIO difference in the recovery of heat-injured cells between the best and worst media. To detect Salmonella in food samples it is essential to repress growth of the competitive microflora. An investigation was carried out on autocytotoxic ~galactosides and ~-glucosides based on the biocide, 8-hydroxyquinoline (8HQ). These substrates might be used to selectively inhibit the competitive microflora. Galactosides were chosen to represent substrates transported into the cell by proton symports, and glucosides because they are representative of substrates transported by the phosphotransferase system (PTS). On hydrolysis 8HQ was released into the cytoplasm, but due to its lipophilicity the biocide migrated into the cytoplasmic membrane. The biocide then diffused into the medium until it reached equilibrium on both sides ofthe membrane. This inhibited .the competitive microflora, but would also inhibit the growth of any Salmonellae present. 8HQ glycosides are unsuitable for use in the pre-enrichment phase. In the next stage of this work glycosides of 8-hydroxyquinoline-5-sulphonic acid (8HQ5S) were synthesised. The sulphonate group is ionised at neutral pH and this ensures that on hydrolysis 8HQ5S remains within the cell. It was found that Klebsiella pneumoniae CMCC3077 could take up 8HQ5S-~,D-galactoside and hydrolyse the substrate, but the biocide did not remain within the cell. It is possible that the free 8HQ5S was exported from the cell by efflux pumps. No activity was found for 8HQ5S-~,Dglucoside. However, no free 8HQ5S was found in the medium. It is unknown whether the cell failed to transport and phosphorylate the substrate through the PTS, or failed to hydrolyse the molecule. As these glycosides failed to meet the requirements for autocytotoxic compounds, work was carried out on alaphosphalin. This is a dipeptide analogue that releases Ll- aminoethylphosphonic acid (AEP) on hydrolysis. AEP inhibits alanine racemase and growth. It was shown that alaphosphalin successfully inhibited K. pneumoniae at various inocula, and it was shown that AEP did not inhibit the recovery of heatinjured Salmonella cells. A major limitation to the use of alaphosphalin is that the peptides in BPW competitively inhibit uptake through the di- and oligo-peptide permeases. However, it is possible to synthesise N-linked glycosides that would be taken up by the glycoside permeases. Dr. Bovill of Thermo Fisher Scientific Ltd., has successfully synthesised AEP-~,D-galactoside. This molecule has been shown to be active against coliform bacteria, but inactive against Salmonella species. This molecule successfully meets all the requirements ofautocytotoxic compounds capable of inhibiting the growth of competitive microflora during the pre-enrichment step during detection of Salmonella spp. in foods.
4

Studies on the Mechanism of Regulation of Amidase Synthesis in Pseudomonas Aeruginosa

Farin, F. 1977 (has links)
No description available.
5

Studies on the autolytic enzymes of bacillus subtilis and clostridium perfringens

Williamson, R. 1978 (has links)
No description available.
6

Organic acids as substrates in microbiology

Ferguson, E. McKay 1977 (has links)
No description available.
7

A study of lysine metabolism in pyricularia oryzae

Thomson, D. M. 1979 (has links)
No description available.
8

Membrane - Bound Enzymes and their Relationship to Membrane Topography in the genus Bacillus

Simpson, R. A. 1975 (has links)
No description available.
9

Studies on the Inhibition of Cell Division by the Antibacterial Compound 5-Diazouracil and Other Treatments

Coates, D. A. 1975 (has links)
No description available.
10

Studies on the biochemistry and physiology of Phaendactylum tricornutum

Glover, H. E. 1974 (has links)
No description available.

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