Thesis (M.S.P.H.)--University of Michigan, 1939.

Thesis (M.S.P.H.)--University of Michigan, 1939.

<p>While the many completely sequenced genomes of bacterial pathogens contain all the determinants of the host-pathogen interaction, and also every possible drug target and recombinant vaccine candidate, computational tools for selecting suitable candidates for further experimental analyses are limited to date. The overall objective of my PhD project was to attempt to design reusable systems that employ the two most important features of bacterial evolution, horizontal gene transfer and adaptive mutation, for the identification of potentially novel virulence-associated factors and possible drug targets. In this dissertation, I report the development of two novel technologies that uncover novel virulence-associated factors and mechanisms employed by bacterial pathogens to effectively inhabit the host niche. More importantly, I illustrate that these technologies may present a reliable starting point for the development of screens for novel drug targets and vaccine candidates, significantly reducing the time for the development of novel therapeutic strategies. Our initial analyses of proteins predicted from the preliminary genomic sequences released by the Sanger Center indicated that a significant number appeared to be more similar to eukaryotic proteins than to their bacterial orthologs. In order determine whether acquisition of genetic material from eukaryotes has played a role in the evolution of pathogenic bacteria, we developed a system that detects genes in a bacterial genome that have been acquired by interkingdom horizontal gene transfer.. Initially, 19 eukaryotic genes were identified in the genome of Mycobacterium tuberculosis of which 2 were later found in the genome of Pseudomonas aeruginosa, along with two novel eukaryotic genes.</p> <p>Surprisingly, six of the M. tuberculosis genes and all four eukaryotic genes in P. aeruginosa may be involved in modulating the host immune response through altering the steroid balance and the production of pro-inflammatory lipids. We also compared the genome of the H37Rv M. tuberculosis strain to that of the CDC- 1551 strain that was sequenced by TIGR and found that the organisms were virtually identical with respect to their gene content, and hypothesized that the differences in virulence may be due to evolved differences in shared genes, rather than the absence/presence of unique genes. Using this observation as rationale, we developed a system that compares the orthologous gene complements of two strains of a bacterial species and mines for genes that have undergone adaptive evolution as a means to identify possibly novel virulence &ndash / associated genes. By applying this system to the genome sequences of two strains of Helicobacter pylori and Neisseria meningitidis, we identified 41 and 44 genes that are under positive selection in these organisms, respectively. As approximately 50% of the genes encode known or potential virulence factors, the remaining genes may also be implicated in virulence or pathoadaptation. Furthermore, 21 H. pylori genes, none of which are classic virulence factors or associated with a pathogenicity island, were tested for a role in colonization by gene knockout experiments. Of these, 61% were found to be either essential, or involved in effective stomach colonization in a mouse infection model. A significant amount of strong circumstantial and empirical evidence is thus presented that finding genes under positive selection is a reliable method of identifying novel virulence-associated genes and promising leads for drug targets.</p>

The sources of gentamicin resistant pseudomonads and enterobacteria were studied in detail. A total of 1703 gentamicin resistant gram negative bacilli (GRGNB) isolated from patients, staff and their immediate environment were studied over a 6 month period . Of these 954 were isolated from clinical specimens obtained from patients and 540 from their immediate environment. A furthur 209 stains were isolated from the staff members who were responsible for the care of these patients. Pseudomonas aeruginosa; pyocin type 1 phage type F7 and .serotype 11 was the commonest isolate. It constituted 24,9% of all isolates in this study. This organism was distributed in all the wards investigated and was isolated throughout the 6 month study period. This strain, therefore, appears to be part of the "resident'' flora of King Edward Vlll Hospital for it was found on patients, staff and their immediate environment. Among the Enterobacteriaceae, Klebsiella pneumoniae was the commonest isolate and made up 13,6 % of all isolates. All the isolates obtained in this study were resistant to five of more antibiotics tested (gentamicin, tobramycin, kanamycin, streptomycin, carberricillin, polymyxin B amikacin and sisomicin). Of 310 staff members screened 25,2% harboured GRGNB on their hands. Among patients the commonest source of GRGNB was stool which yielded 141 (14,8 %) of the clinical isolates. Of the environmental sources studied, sinks harboured 87 (14%) GRGNB. The isolates from the environment and staff members were identical to patient strains. The significance of these findings is discussed. / Thesis (Fellowship of the Society of Medical Laboratory Technologists of South Africa)-University of Natal, Durban, 1985.

A survey was conducted to answer two basic questions: 1) What are the medical bacteriology laboratories of Indiana using as criteria for identifying microorganisms? and 2) What is the basis for these criteria? The author developed a questionnaire used as the survey instrument. One hundred fifty questionnaires were mailed to medical laboratories throughout Indiana. Sixty percent of the laboratories responded. This study lists all responses and gives a description and/or evaluation of each procedure.In addition, the researcher discusses some of the factors influencing the type of procedures that are being used. Data collected by this research will be submitted to the biology department at Ball State University to help establish more concrete guidelines that can be used to update course content.

<p>While the many completely sequenced genomes of bacterial pathogens contain all the determinants of the host-pathogen interaction, and also every possible drug target and recombinant vaccine candidate, computational tools for selecting suitable candidates for further experimental analyses are limited to date. The overall objective of my PhD project was to attempt to design reusable systems that employ the two most important features of bacterial evolution, horizontal gene transfer and adaptive mutation, for the identification of potentially novel virulence-associated factors and possible drug targets. In this dissertation, I report the development of two novel technologies that uncover novel virulence-associated factors and mechanisms employed by bacterial pathogens to effectively inhabit the host niche. More importantly, I illustrate that these technologies may present a reliable starting point for the development of screens for novel drug targets and vaccine candidates, significantly reducing the time for the development of novel therapeutic strategies. Our initial analyses of proteins predicted from the preliminary genomic sequences released by the Sanger Center indicated that a significant number appeared to be more similar to eukaryotic proteins than to their bacterial orthologs. In order determine whether acquisition of genetic material from eukaryotes has played a role in the evolution of pathogenic bacteria, we developed a system that detects genes in a bacterial genome that have been acquired by interkingdom horizontal gene transfer.. Initially, 19 eukaryotic genes were identified in the genome of Mycobacterium tuberculosis of which 2 were later found in the genome of Pseudomonas aeruginosa, along with two novel eukaryotic genes.</p> <p>Surprisingly, six of the M. tuberculosis genes and all four eukaryotic genes in P. aeruginosa may be involved in modulating the host immune response through altering the steroid balance and the production of pro-inflammatory lipids. We also compared the genome of the H37Rv M. tuberculosis strain to that of the CDC- 1551 strain that was sequenced by TIGR and found that the organisms were virtually identical with respect to their gene content, and hypothesized that the differences in virulence may be due to evolved differences in shared genes, rather than the absence/presence of unique genes. Using this observation as rationale, we developed a system that compares the orthologous gene complements of two strains of a bacterial species and mines for genes that have undergone adaptive evolution as a means to identify possibly novel virulence &ndash / associated genes. By applying this system to the genome sequences of two strains of Helicobacter pylori and Neisseria meningitidis, we identified 41 and 44 genes that are under positive selection in these organisms, respectively. As approximately 50% of the genes encode known or potential virulence factors, the remaining genes may also be implicated in virulence or pathoadaptation. Furthermore, 21 H. pylori genes, none of which are classic virulence factors or associated with a pathogenicity island, were tested for a role in colonization by gene knockout experiments. Of these, 61% were found to be either essential, or involved in effective stomach colonization in a mouse infection model. A significant amount of strong circumstantial and empirical evidence is thus presented that finding genes under positive selection is a reliable method of identifying novel virulence-associated genes and promising leads for drug targets.</p>

Philosophiae Doctor - PhD (Biochemistry) / While the many completely sequenced genomes of bacterial pathogens contain all the determinants of the host-pathogen interaction, and also every possible drug target and recombinant vaccine candidate, computational tools for selecting suitable candidates for further experimental analyses are limited to date. The overall objective of my PhD project was to attempt to design reusable systems that employ the two most important features of bacterial evolution, horizontal gene transfer and adaptive mutation, for the identification of potentially novel virulence-associated factors and possible drug targets. In this dissertation, I report the development of two novel technologies that uncover novel virulence-associated factors and mechanisms employed by bacterial pathogens to effectively inhabit the host niche. More importantly, I illustrate that these technologies may present a reliable starting point for the development of screens for novel drug targets and vaccine candidates, significantly reducing the time for the development of novel therapeutic strategies. Our initial analyses of proteins predicted from the preliminary genomic sequences released by the Sanger Center indicated that a significant number appeared to be more similar to eukaryotic proteins than to their bacterial orthologs. In order determine whether acquisition of genetic material from eukaryotes has played a role in the evolution of pathogenic bacteria, we developed a system that detects genes in a bacterial genome that have been acquired by interkingdom horizontal gene transfer.. Initially, 19 eukaryotic genes were identified in the genome of Mycobacterium tuberculosis of which 2 were later found in the genome of Pseudomonas aeruginosa, along with two novel eukaryotic genes.Surprisingly, six of the M. tuberculosis genes and all four eukaryotic genes in P. aeruginosa may be involved in modulating the host immune response through altering the steroid balance and the production of pro-inflammatory lipids. We also compared the genome of the H37Rv M. tuberculosis strain to that of the CDC- 1551 strain that was sequenced by TIGR and found that the organisms were virtually identical with respect to their gene content, and hypothesized that the differences in virulence may be due to evolved differences in shared genes, rather than the absence/presence of unique genes. Using this observation as rationale, we developed a system that compares the orthologous gene complements of two strains of a bacterial species and mines for genes that have undergone adaptive evolution as a means to identify possibly novel virulence &ndash;associated genes. By applying this system to the genome sequences of two strains of Helicobacter pylori and Neisseria meningitidis, we identified 41 and 44 genes that are under positive selection in these organisms, respectively. As approximately 50% of the genes encode known or potential virulence factors, the remaining genes may also be implicated in virulence or pathoadaptation. Furthermore, 21 H. pylori genes, none of which are classic virulence factors or associated with a pathogenicity island, were tested for a role in colonization by gene knockout experiments. Of these, 61% were found to be either essential, or involved in effective stomach colonization in a mouse infection model. A significant amount of strong circumstantial and empirical evidence is thus presented that finding genes under positive selection is a reliable method of identifying novel virulence-associated genes and promising leads for drug targets. / South Africa

Thesis (Master of Applied Sciences in Chemistry)--Cape Peninsula University of Technology, 2018. / Maintenance of optimum wound chemistry is important to ensure timely healing of a wound. Bacterial infections impair the process of wound healing by producing toxins that alter the chemical environment in and around the wound. The imbalance in the wound chemistry prolongs healing and opens doors to opportunistic infections. Bacteria have developed resistance to conventional bactericides hence, there is need for search of new bactericides that can control bacteria in and around the wound. Therefore, new chemical or biochemical bactericides, which are not resisted by the bacteria, can be explored to control bacterial life around the wound in a bid to maintain optimum wound healing chemistry. Materials such as chitosan, zinc oxide, copper oxide and silver have showed remarkable potential as both bactericidal and wound healing agents. In this work silver, zinc oxide, and copper oxide nanoparticles (NPs) and their chitosan composites (CH-NPs) were synthesized using the chemical reduction method and simple chelation respectively to produce nanoparticles of Ag, ZnO, and CuO as well as composites of CH-ZnO, CH-Ag, CH-CuO, and CH-ZnO-Ag-CuO. Formation of the NPs was confirmed by the exhibition of characteristic peaks in UV-Visible and Fourier Transform Infrared Resonance (FTIR) spectroscopy as well as X-ray diffraction. The nanoparticles (NPs) had optical and electronic band gaps in the range 1 to 5eV indicating their semi-conductive nature. X-ray diffraction (XRD) investigations depicted the crystalline structures of the NPs to be base-centred, face-centred, and hexagonal for Ag, CuO, and ZnO respectively. Transmission electron microscopy (TEM) studies exhibited spherical, hexagonal, and rod-shaped shapes for silver, copper oxide, zinc oxide NPs respectively. Electrochemical investigations of the pure NPs indicated the existence of both the adsorption and the diffusion controlled electron transfer processes at electrode surfaces as well as fast electron transfer rate as depicted by the charge transfer coefficient and standard rate constant parameter values. FTIR spectra of CH-NPs composites depicted new excitation bands absent in spectra of both chitosan and the NPs. The spectra also indicated the deformation and absence of the amine (-NH2) and hydroxyl bands (-OH) within the CH-NPs composites. UV-Visible spectroscopy investigations of the CH-NPs composites exhibited blue-shifts of the λmax with respect to the NPs. The FTIR and UV-Visible spectra confirmed the existence of bonding between the chitosan and the NPs. The optical band gap energies of all the CH-NPs composites fell within the range of 2.0 to 4.5 eV indicating that the CH-NPs fell in the category of the semi-conducting materials after chelating with the chitosan.

This study of four domestic abattoirs in South Australia with Quality Assurance programmes in place established the size of bacterial populations that could be expected on pig carcasses on entry to abattoir dressing floors at pre-evisceration, the extent of contamination occurring during carcass dressing, and the effect of chilling on these populations. Analysis was conducted for salmonellae, Escherichia coli, Total Viable Count, and pseudomonads. Exterior swabbing was compared to swabbing of corresponding interior sites which are sterile initially. The interior swabbing sites were found to be a more reliable measure of contamination during the dressing process than the swabbing of already contaminated exterior sites. During the identification of some of the points of carcass contamination, the effectiveness of end-of-work foam cleaning programmes used at abattoir dressing floors and their relationship to the potential for airborne contamination of carcasses was examined and found to be positive. Operators' work tools and hands were identified as sources of interior carcass contamination combined with failure of operators to adhere to Standard Operating Procedures (SOPs) during carcass dressing, especially those related to hand and forearm washing at appropriate times. Foot-operated full-immersion hot water units for operators' knives and steels were designed and installed at two abattoirs to give operators access to physically and biologically clean work tools throughout carcass dressing. / PhD Doctorate

Univ., Habil.-Schr. u.d.T.: Gradmann, Christoph: Medizin und Mikrobiologie in Deutschland 1870 - 1910--Heidelberg, 2001. / Literaturverz. S. 347 - [370].