Iron is an essential nutrient that is sequestered by iron-binding proteins in the human host resulting in a hostile environment for microbes. Neisseria gonorrhoeae, however, can utilize numerous iron-binding proteins such as transferrin and lactoferrin to acquire this nutrient. During initial infection, gonococci have access to transferrin and lactoferrin present in semen and vaginal fluids, as well as to hemoglobin present in blood during menses or disseminated infections. Consequently, the gonococcus likely encounters conditions of high iron at some stages in the course of natural infection. Potential contributions of iron to gonococcal invasion have however been largely over looked in the field as most studies investigating invasion represent iron depleted environments. Considering the link between menses in women and ascending gonococcal infections, we hypothesized that high iron concentrations present at this time triggers the induction of membrane proteins that enhance gonococcal pathogenesis. Here, we report the gonococcal iron-induced surface proteome and show evidence of post-translational modification of many of these proteins. We also present evidence of an iron enhanced, Opa-independent invasion mechanism. Finally, we investigated the role of NspA, TdfJ and NGO1063 on Opa-independent iron induced invasion. Our studies underscore the importance of investigating the effect of iron on gonococcal host cell interactions. Given the potential clinical relevancy of this phenomenon, data from our studies represent a solid framework for further investigation of gonococcal pathogenesis.

Includes bibliographical references. / 3 v. var. pagings. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Comprises 171 published works on the general theme of bacterial cell surfaces and pathogenesis. Seeks to address important areas facing medical research by the application of bacterial genetics and molecular biology. The common goal is to provide a better understanding of the mechanisms of pathogenesis of the diseases and how these pathogens have evolved such that this information might be applied to vaccine design and diagnosis. / Thesis (D.Sc.)--University of Adelaide, Dept. of Microbiology and Immunology, 2000?

No description available.

Includes bibliographical references. / 3 v. var. pagings. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Comprises 171 published works on the general theme of bacterial cell surfaces and pathogenesis. Seeks to address important areas facing medical research by the application of bacterial genetics and molecular biology. The common goal is to provide a better understanding of the mechanisms of pathogenesis of the diseases and how these pathogens have evolved such that this information might be applied to vaccine design and diagnosis. / Thesis (D.Sc.)--University of Adelaide, Dept. of Microbiology and Immunology, 2000?

Thesis (D.Sc.)--University of Adelaide, Dept. of Microbiology and Immunology, 2000? / Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 53-57).

<p>Originally considered the sole providence of protein coding sequences, evolutionary biology has begun to recognize the importance of non-coding DNA in dictating phenotypic adaptation. Exclusively examined in eukaryotic anatomical development, <em>cis</em>-regulatory modifications have the power to alter the spatial-temporal dynamics of gene expression without the plieotropic consequences of protein modification. Owing to the need to integrate horizontally acquired DNA into existing regulatory networks, <em>cis</em>-regulatory mutations may also significantly contribute to prokaryotic evolution. The horizontal acquisition of <em>Salmonella</em> Pathogenicity Island (SPI)-2 led to the evolutionary divergence of <em>Salmonella enterica</em> from <em>S. bongori</em>. Use of the type 3 secretion system encoded in SPI-2 allowed <em>S. enterica</em> to exploit an intracellular host niche offered by immune cells and allowed for its systemic dissemination. Here we identify ancestrally encoded <em>srfN</em> and <em>dalS</em> and demonstrate that through acquisition of a binding site for the SPI-2 regulator, SsrB, they have contributed to the pathoadaptation of <em>S. enterica</em> to the host environment. We also demonstrate that ancestral regulatory networks contribute to the establishment of an expression hierarchy for SPI-2 <em>in vitro</em> and to transcriptional priming in the host lumen prior to invasion. These findings demonstrate that <em>cis</em>-regulatory modifications have significantly contributed to the evolution of <em>S. enterica</em> as an intracellular pathogen.</p> / Doctor of Philosophy (PhD)

A probability matrix for computer-assisted identification of vibrios has been constructed, based on the API20E system. Data were gathered from 173 strains representing 31 taxa of vibrios and related organisms, from a variety of sources. The matrix was tested internally by four statistical programs. Program OVERMAT and program MOSTTYP tested the separation and homogeneity of the taxa. Most of the taxa were satisfactory but a few were less so; reasons for this are discussed. Program CHARSEP and program DIACHAR tested the separation and diagnostic values, respectively, of the 50 characters used and from the results a shorter diagnostic test set was drawn up. The overall test error rate was 4.5%. The matrix was assessed externally by its performance in the identification of vibrio-like strains isolated from freshwater. The overall success rate for identification was 84%, using a Willcox score of ?0.99. The data generated for 172 of the reference strains and 243 wild strains were subjected to numerical taxonomic analysis. The main purpose of these analyses was to verify the quality of the identification scheme. Nevertheless the results produced were in good agreement with those of more detailed taxonomic studies. The taxonomic position of some named and some unnamed groups of Vibrio and Aeromonas was clarified, and taxa showing poor distinction were highlighted. An ecological survey was carried out to determine the distribution and seasonal occurrence of vibrios in various freshwater sites in the U.K. The results showed that species of vibrio both pathogenic and non-pathogenic for man, are widely distributed in rivers and canals. Some of the species considered to be indigenous to the waters. The role of these organisms in the freshwater environment remains to be determined.

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No description available.