FUNCTIONAL CHARACTERIZATION OF THE LINK BETWEEN CARBOHYDRATE METABOLISM AND THE PATHOGENESIS OF THE INVASIVE M1T1 GROUP A STREPTOCOCCUS

The Group A Streptococcus (GAS), or Streptococcus pyogenes, is a strict human pathogen that colonizes a variety of sites within the host. Infections can vary from minor and easily treatable, to life-threatening, invasive forms of disease. In order to adapt to niches, GAS utilizes environmental cues, such as carbohydrates, to coordinate the expression of virulence factors. Research efforts to date have focused on identifying how either components of the phosphoenolpyruvate-phosphotransferase system (PTS) or global transcriptional networks affect the regulation of virulence factors, but not the synergistic relationship between the two. The present study investigates the role of a putative PTS-fructose operon encoded by fruRBA and its role in virulence in the M1T1 strain 5448. Growth in fructose resulted in induction of fruRBA. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose. Growth and carbon utilization profiles revealed that although the entire fruRBA operon was required for growth in fructose, FruA was the main fructose transporter. The ability of both ΔfruR and ΔfruB mutants to survive in whole human blood or neutrophils was impaired. However, the phenotypes were not reproduced in murine whole blood or in a mouse intraperitoneal infection, indicating a human-specific mechanism. While it is known that the PTS can affect activity of the Mga virulence regulator, further characterization of the mechanism by which sugars and its protein domains affect activity have not been studied. Transcriptional studies revealed that the core Mga regulon is activated more in a glucose-rich than a glucose-poor environment. This activation correlates with the differential phosphorylation of Mga at its PTS regulatory domains (PRDs). Using a 5448 mga mutant, transcriptome studies in THY or C media established that the Mga regulon reflects the media used. Interestingly, Mga regulates phage-encoded DNases in a low glucose environment. We also show that Mga activity is dependent on C-terminal amino acid interactions that aid in the formation of homodimers. Overall, the studies presented sought to define how external environmental cues, specifically carbohydrates, control complex regulatory networks used by GAS, contribute to pathogenesis, and aid in adaptation to various nutrient conditions encountered.

The relationship between health literacy and indicators of informed decision making for colorectal cancer screening among African Americans

African Americans are disproportionately affected by colorectal cancer (CRC) incidence and mortality. CRC early detection leads to better treatment outcomes and, depending on the screening test, can prevent the development of CRC. African Americans, however, are screened less often than Whites. Aspects of decision making (e.g., decisional conflict, decision self-efficacy) can impact decision making outcomes and may be influenced by social determinants of health, including health literacy. However the relationship between social determinants of health and indicators of decision making in this population is not fully understood. Additionally, individuals have a choice between different CRC screening tests and an individual’s desire to use a particular screening test may be associated with social determinants of health such as health literacy. This study aimed to examine the relationship between social determinants of health and indicators of decision making for CRC screening among African Americans. A total of 111 participants completed a baseline and 14-month follow-up survey assessing decisional conflict, decision self-efficacy, decisional preference (shared versus informed decision making), and CRC test preference. Health literacy was negatively associated with decisional conflict and positively associated with decision self-efficacy (ps < .05). Individuals who were unemployed or working part-time had significantly greater decisional conflict than individuals working full-time (ps < .05). Individuals with a first-degree family history of CRC had significantly lower decision self-efficacy than individuals without a family history (p < .05). Women were significantly more likely to prefer making a shared decision rather than an informed decision compared to men (p < .05). Lastly, previous CRC screening behavior was significantly associated with CRC test preference (e.g., individuals previously screened using colonoscopy were significantly more likely to prefer colonoscopy for their next screening test; ps < .05). These findings begin to identify social determinants of health (e.g., health literacy, employment) that are related to indicators of decision making for CRC among African Americans. Furthermore, these findings suggest further research is needed to better understand these relationships to help with the future development and improvement of interventions targeting decision making outcomes for CRC screening in this population.

Civil Rights on the Cell Block: Race, Reform, and Violence in Texas Prisons and the Nation, 1945-1990

This study, "Civil Rights on the Cell Block: Race, Reform, and Violence in Texas Prisons and the Nation, 1945-1990," offers a new perspective on the historical origins of the modern prison industrial complex, sexual violence in working-class culture, and the ways in which race shaped the prison experience. This study joins new scholarship that reperiodizes the Civil Rights era while also considering how violence and radicalism shaped the civil rights struggle. It places the criminal justice system at the heart of both an older racial order and within a prison-made civil rights movement that confronted the prison's power to deny citizenship and enforce racial hierarchies. By charting the trajectory of the civil rights movement in Texas prisons, my dissertation demonstrates how the internal struggle over rehabilitation and punishment shaped civil rights, racial formation, and the political contest between liberalism and conservatism. This dissertation offers a close case study of Texas, where the state prison system emerged as a national model for penal management. The dissertation begins with a hopeful story of reform marked by an apparently successful effort by the State of Texas to replace its notorious 1940s plantation/prison farm system with an efficient, business-oriented agricultural enterprise system. When this new system was fully operational in the 1960s, Texas garnered plaudits as a pioneering, modern, efficient, and business oriented Sun Belt state. But this reputation of competence and efficiency obfuscated the reality of a brutal system of internal prison management in which inmates acted as guards, employing coercive means to maintain control over the prisoner population. The inmates whom the prison system placed in charge also ran an internal prison economy in which money, food, human beings, reputations, favors, and sex all became commodities to be bought and sold. I analyze both how the Texas prison system managed to maintain its high external reputation for so long in the face of the internal reality and how that reputation collapsed when inmates, inspired by the Civil Rights Movement, revolted. My dissertation shows that this inmate Civil Rights rebellion was a success in forcing an end to the existing system but a failure in its attempts to make conditions in Texas prisons more humane. The new Texas prison regime, I conclude, utilized paramilitary practices, privatized prisons, and gang-related warfare to establish a new system that focused much more on law and order in the prisons than on the legal and human rights of prisoners. Placing the inmates and their struggle at the heart of the national debate over rights and "law and order" politics reveals an inter-racial social justice movement that asked the courts to reconsider how the state punished those who committed a crime while also reminding the public of the inmates' humanity and their constitutional rights.