Thesis (M.S.)--University of Wisconsin--Madison, 1963. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 131-138)

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Thesis(M.S.)--Auburn University, 2006. / Abstract. Vita. Includes bibliographic references.

Thesis (M.S.)--University of Wyoming, 2007. / Title from PDF title page (viewed on Nov. 7, 2008). Includes bibliographical references (p. 30-35).

Thesis (Ph. D.)--Auburn University, 2008. / Abstract. Vita. Includes bibliographical references (p. 83-89).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1947. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The vaginal microbiome plays an important role in reproductive health and pregnancy. It has coevolved with humans and has direct effects on reproductive success, rendering selective pressure more pronounced at this site. Herein, we probe coevolution of the vaginal microbiome using a systems-level approach. In Chapter 2, we examine the evolutionary trajectory of two vaginal Veillonellaceae phylotypes evolved from an ancestral gastrointestinal lineage to inhabit the vaginal niche. We present evidence of their divergence and subniche specification and describe their differential associations with vaginal infection and pregnancy. In Chapter 3, we identify ten bacterial taxa, predicted to contribute to the underlying pathology of the sexually transmitted infection trichomoniasis. This ‘pathogroup’, which has undergone conditional differentiation to thrive in the presence of T. vaginalis, includes previously undescribed organisms and putative symbionts. Lastly in Chapter 4, we present the first characterization of BspA proteins, multi-modal virulence factors, in the vaginal microbiome and provide evidence of their extensive horizontal transfer across diverse microbial lineages. We use homology modeling to demonstrate conservation of structural and functional characteristics of these proteins between diverse bacterial taxa and identify structural variants, potentially indicative of subtypes. These findings further our understanding of the contributions of individual bacterial species, bacterial communities and virulence determinants in the health and disease. Furthermore, they lay the groundwork for future work characterizing coevolution of the human vaginal microbiome. These systems-level approaches will facilitate synergy between broad and reductive approaches and inform strategies for modulation of the microbiome and development of more effective therapeutics.

Dicationic diamidines synthesized in the Boykin group a have shown broad range of activity against a wide variety of microbial pathogens such as Cryptosporidium parvum, Leishmania donovani, Plasmodium falciparum, Trypanosoma burcei, and Trichomonas vaginalis. Thiophene based dicationic diamidines have been especially impressive versus Trichomoniasis, and several species of the leishmania parasite. The best compound in vitro against leishmania was 2,5-bis-(4-amidophenyl)thiophene [DB 351]. In an attempt to improve upon antileishmanial activity, several analogs of DB 351 have been synthesized. Previously the central heterocyclic ring has been changed (furan, pyrrole, etc.), and the phenyl has been substituted with a pyridine ring, however, in the thiophene series, the 3 and 4 position of the central thiophene ring has remained unmodified. By modifying the 3 and 4 position of the thiophene ring, and taking advantage of the substituent effect, the pharmacodynamic and distribution properties of DB 351 will altered; hopefully leading to more potent antileishmanial compounds.

Dicationic diamidines synthesized in the Boykin group a have shown broad range of activity against a wide variety of microbial pathogens such as Cryptosporidium parvum, Leishmania donovani, Plasmodium falciparum, Trypanosoma burcei, and Trichomonas vaginalis. Thiophene based dicationic diamidines have been especially impressive versus Trichomoniasis, and several species of the leishmania parasite. The best compound in vitro against leishmania was 2,5-bis-(4-amidophenyl)thiophene [DB 351]. In an attempt to improve upon antileishmanial activity, several analogs of DB 351 have been synthesized. Previously the central heterocyclic ring has been changed (furan, pyrrole, etc.), and the phenyl has been substituted with a pyridine ring, however, in the thiophene series, the 3 and 4 position of the central thiophene ring has remained unmodified. By modifying the 3 and 4 position of the thiophene ring, and taking advantage of the substituent effect, the pharmacodynamic and distribution properties of DB 351 will altered; hopefully leading to more potent antileishmanial compounds.