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Graduate Degree Program in Cell & Molecular Biology

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https://hdl.handle.net/10217/100362
These digital collections include theses, dissertations, and faculty publications from the Graduate Degree Program in Cell & Molecular Biology.

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Browsing Graduate Degree Program in Cell & Molecular Biology by Author "Abdo, Zaid, advisor"

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    Influence of management practices on virulence factors, antimicrobial resistance genes and heavy metal resistance genes in broiler chicken production
    (Colorado State University. Libraries, 2023) Woyda, Reed Richard, author; Abdo, Zaid, advisor; Oladeinde, Adelumola, committee member; Daniels, Josh, committee member; Sloan, Dan, committee member; Stenglein, Mark, committee member
    The main bacterial species associated with food-borne illness in humans are Escherichia coli, Salmonella species and Campylobacter species. The ability of a bacterial strain to survive the food-production pipeline and to mount an infection and cause disease in humans is dependent on an array of genetic factors. The presence of specific virulence factors will influence the severity of disease while antimicrobial resistance genes affect the choice and efficacy of treatment. Management practices in poultry production aim at reducing the incidence of poultry and human bacterial pathogens and, in general, at maintaining a healthy flock and a healthy global population. However, the influence of management practices, in a post-antibiotic era, on pathogenic bacterial species, and in particular the selective pressures imposed on genetic factors such as antimicrobial and metal resistance and virulence factors, are understudied. In Chapter 2, we provide a robust bacterial genomic analysis pipeline which is used for subsequent analysis in the following chapters. Chapter 3 provides an understanding of the current antimicrobial resistance and virulence factors present in chicken production and human clinical settings. This work found these host sources harbored different antimicrobial resistance genes and virulence factors that can classify them into phylogroups and host origin. In Chapter 4, through characterization of Campylobacter species isolated from broiler litter, we determined the reused litter environment selected for Campylobacter species lacking virulence factors aiding in colonization of chicken and human hosts. In Chapter 5, we determined the practice of adding copper sulfate to drinking water, commonly used for growth promotion or sanitization, may have selected for, and provided a reservoir for, Salmonella strains harboring plasmid-borne copper resistance genes. Overall, this work provides a computational pipeline for the high-throughput analysis of bacterial genomes and provides insights into selective pressures imposed on pathogenic bacterial species by modern-day management practices.
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    Of microbes and mothers: evaluating the complex maternal-neonatal interaction and microbiome-immunity development with novel Lactobacillus vaccination
    (Colorado State University. Libraries, 2024) Ecton, Kayl E., author; Abdo, Zaid, advisor; Dean, Gregg, advisor; Wrighton, Kelly, committee member; Vilander, Allison, committee member; Argueso, Lucas, committee member
    The task of identifying an optimal vaccination strategy for neonates has been challenging scientists and physicians alike. Multiple factors contribute to the difficulty in establishing an optimal platform including the complexity of the maternal-fetal dyad, a neonatal Th2 skewed profile and the role of the parallel development of the immune system and the gut microbiome (8). Disease remains a main cause of infant morbidity and mortality, encouraging the discovery of novel infant vaccinations to be delivered during the first 28 days of life to provide protection (41). Passive protection from the maternal transfer of transplacental IgG and both IgG and IgA in breastmilk has a limited window of operation, leaving the maturing neonate at risk (128). Although exact mechanisms remain to be elucidated, here we examine the complex crosstalk between mother-fetus and maternal-neonate dyads, neonatal microbiome-immunity development, and optimal delivery strategies for neonatal vaccine development. In this dissertation we investigated the role of maternal infection prior to gestation, neonatal challenge after vaccination, and vaccine effectiveness after exposure to virus. We evaluated the use of a novel vaccine platform developed previously in the lab as an orally delivered mucosal targeting subunit vaccine in Lactobacillus acidophilus. We investigated the effectiveness of the recombinant vaccine with and without adjuvants in a neonatal experimental design model and discovered increased virus specific responses in neonates vaccinated with adjuvants when challenged with rotavirus. We show a significant impact of maternal influence on neonatal outcomes. Beyond the immunogenic strength of the novel Lactobacillus acidophilus vaccine platform in neonates, we identified induced shifts to the gut microbial communities that occurred with vaccination or infection. We saw a shift in the gut microbiome over the course of a 7-day rotavirus challenge in neonates that did not return to baseline during the observation period, even after no virus shedding was detected in fecal samples. We also evaluated the impact of different doses, 1x106 CFU/dose and 1x109 CFU/dose, on the immune response and the gut microbiome. We confirmed the role of fecal microbiome transplants in breeding does to normalize for the maternal microbiome prior to gestation. Our results indicate that there are modifications to the gut microbiome and changes in immune antibodies during vaccination and infection. While we did not pursue a specific mechanism crosslinking the maternal-neonatal interaction and the gut-immunity relationship, we do consider the presence of such a connection.