Zugl.: Giessen, Univ., Diss., 2004. / Computerdatei im Fernzugriff.

Zugl.: Giessen, Universiẗat, Diss., 2004.

A dissertation submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, for the degree of Master of Science in Medicine. / Analysis of organisms involved in hospital infections has shown that Gram-positive bacteria have assumed an increasingly important role. Examples that have been recognised as important pathogens are staphylococci , enterococci, streptococci, Corynebacterium jeikeium and Leuconostoc species. Methicillin resistance in staphylococci has become a major problem in certain hospitals. Viridans streptococci continue to be the most frequent cause of native valve endocarditis. Leuconostoc species are being increasingly isolated from blood cuIture specimens. strains of Gram-positive bacteria have become resistant to specific antibiotics; e.g. staphylococci to methicillin, enterococci to ampicillin, and viridans streptococci to penicillin. JK corynebacteria are sensitive only to vancomycin and resistant to other antimicrobials normally used for treating infection caused by Gram-positive bacteria. In this study various combinations of antimicrobials against 35 clinical isolates of Gram-positive bacteria obtained from three hospitals in the Johannesburg area (Johannesburg, Hillbrow, and Baragwanath) from 1987- 1988 were investigated. The MIC / MBC results conformed to others described in worldwide studies. Results when different methodologies for determining synergy were used, varied. This emphasizes the need for standardization, especially with regard to the time-kill studies. Most antimicrobial combinations demonstrated tested against Leuconostoc species synergy using the checkerboard method, but these results were not confirmed by time-kill procedures, which showed mainly indifference. Synergy was also obtained when gentamicin plus ciprofloxacin was combined Corynebacterium jeikeium. Because of increasing resistance and the fact that Gram- positive bacteria cause serious infections, various and new combinations of antimicrobials need to be tested before treating these infections. Parts of this dissertation have been presented at the following congresses: 10th Annual Congress of the Society of Medical. Laboratory Technologists of South Africal Sun city 1989 75th Anniversary Congress of Pathology Johannesburg 1990 11th Annual Congress of the Society of Medical Laboratory Technologists of South Africa, Durban 1991 / Andrew Chakane 2019

Braunschweig, Techn. Universiẗat, Diss., 1999.

Düsseldorf, Universiẗat, Diss., 2003.

No description available.

München, Techn. Univ., Diss., 2010. / Zsfassung in dt. Sprache.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Bacteriophage (phage), virus of bacteria, has been proposed as a mean to inactivate bacteria that are pathogens of humans. Applied prophylatically to food, phage might decrease the numbers of potential pathogens we ingest. Much active research on using the phages of bacteria to control Gram negative foodborne pathogens are described in the literatures, but comparatively little research describes the phages of Gram positive bacteria and their use as biocontrol agents on food. In this work, previous undescribed phages, able to infect Bacillus cereus and Listeria monocytogenes, were isolated from soil and ruminants faecal material, respectively. As the first step in assessing their potential as biocontrol agents, the isolated phages were purified, concentrated and characterised (albeit to different degrees). The Bacillus phages had a narrow host range while the Listeria phages had a broad host range. Listeria phages also infected L. monocytogenes 2000/47, a strain which recurs in New Zealand clinical cases. Both Bacillus and Listeria phages appeared to be of the Myoviridae family judging by their structure in electron micrographs. The Bacillus FWLBc1 and FWLBc2 phages were lytic phages with a latent period of 106 and 102 min at 37°C, and an average burst size of 322 and 300 phages per infected cell, respectively. Moreover, they both had genomes of approximately 134 kb. All newly isolated and characterized phages were chloroform resistant and survived storage better at 4°C than at room or freezing temperatures. Bacillus phages significantly reduced the bacterial population in mashed potatoes within 24 h at room temperature, when applied at a phage to host ratio of 1000. Listeria phages rapidly inactivated the host population to a low optical density. The findings of this thesis will add to the current knowledge of phages in the context of various environmental conditions for different bacteria and will demonstrate the potential of phages as food safety biocontrol agents.

Tetrodecamycin (1) is a novel α-(γ-hydroxyacyl) tetronic acid based polyketide antibiotic isolated from the culture broth of Streptomyces nashvillensis MJ885-mF8 by Takeuchi et al. in 1994. Compound 1 shows potent inhibitory activity against Gram-positive bacteria including Bacillus anthracis and methicillin resistant Staphylococcus aureus (MRSA). It was proposed that an Aldol reaction of trans-decalin core 2 and tetronic acid derivative 3 followed by a face selective epoxidation and a subsequent epoxide-opening reaction would deliver the 6,6,7,5-skeleton of tetrodecamycm (1). To investigate this proposal, the silyl enol ether 5 was prepared from cycloheptene 4 in 7 steps. An unusual domino silyl enol ether reaction sequence was observed when the silyl enol ether 5 was submitted to a Diels-Alder reaction. It afforded cycloadduct 6, which was converted to the key intermediate 2 after another 3 steps (Scheme 1). Concurrently, double functionalisation of simple cyclic silyl enol ethers was investigated. Because of some difficulties in reproducing good overall yields to the cycloadduct 6, a second synthetic route was proposed. It was envisaged that a palladium-catalysed oxidative cyclisation or an organoselenium-mediated cyclisation reaction of compound 8 would construct the 6,6,7,5- skeleton 7, which would be converted to tetrodecamycin (1) via dihydroxylation followed by an introduction of the exo-methylene group. The intramolecular Diels-Alder reaction of trienal 11 afforded trans-decalin 10, which was converted to β-keto ester 9 in 2 steps. A Dieckmann-type cyclisation of 9 afforded compound 8 in good yield. However, so far transformation to compound 7 has not been achieved (Scheme 2).