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Browsing 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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    Microbes in the mucosa: impacts of the mucosal immune system and oral vaccination with Lactobacillus acidophilus on the gut microbiome
    (Colorado State University. Libraries, 2021) Fox, Bridget E., author; Dean, Gregg, advisor; Abdo, Zaid, advisor; Tobet, Stuart, committee member; Ryan, Elizabeth, committee member
    The mucosal immune system is constantly balancing between the clearance of pathogens, tolerance of self-antigen and food, and maintenance of homeostasis within the microbiota. Vaccination via mucosal routes is advantageous because it provides protection at local mucosal sites and systemically. However, induction of efficacious responses are often difficult due to the inherent barriers of the mucosal tissues. We have developed a probiotic-based mucosal vaccination platform that utilizes recombinant Lactobacillus acidophilus (rLA) to overcome these obstacles presented in oral vaccination. Here, we sought to determine whether repeated administration of rLA alters the intestinal microbiome as a result of L. acidophilus probiotic activity (direct competition and selective exclusion) or from the host's mucosal immune response against the rLA vaccine. To address the latter, IgA-seq was employed to characterize shifts in IgA-bound bacterial populations. Additionally, we determined whether using rice bran as a prebiotic would influence the immunogenicity of the vaccine and/or IgA bound bacterial populations. Our results show that the prebiotic influenced the kinetics of rLA antibody induction, and that the rLA platform does not cause lasting disturbances to the microbiome. Nucleotide-binding oligomerization domain containing 2 (NOD2) has presented itself as an essential regulator of immune responses within the gastrointestinal tract. This innate immune receptor is expressed by several cell types, including both hematopoietic and nonhematopoietic cells within the gastrointestinal tract. Mice harboring knockouts of NOD2 only in CD11c+ cells were used to better characterize NOD2 signaling during mucosal vaccination with rLA. We show that NOD2 signaling in CD11c+ cells is critical for mounting a humoral immune response against rLA. Additionally, disruption of NOD2 signaling in CD11c+ cells results in an altered bacterial microbiome profile in both vaccinated and unvaccinated mice.
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    Modern considerations for the use of naive Bayes in the supervised classification of genetic sequence data
    (Colorado State University. Libraries, 2021) Lakin, Steven M., author; Abdo, Zaid, advisor; Rajopadhye, Sanjay, committee member; Stenglein, Mark, committee member; Stewart, Jane, committee member
    Genetic sequence classification is the task of assigning a known genetic label to an unknown genetic sequence. Often, this is the first step in genetic sequence analysis and is critical to understanding data produced by molecular techniques like high throughput sequencing. Here, we explore an algorithm called naive Bayes that was historically successful in classifying 16S ribosomal gene sequences for microbiome analysis. We extend the naive Bayes classifier to perform the task of general sequence classification by leveraging advancements in computational parallelism and the statistical distributions that underlie naive Bayes. In Chapter 2, we show that our implementation of naive Bayes, called WarpNL, performs within a margin of error of modern classifiers like Kraken2 and local alignment. We discuss five crucial aspects of genetic sequence classification and show how these areas affect classifier performance: the query data, the reference sequence database, the feature encoding method, the classification algorithm, and access to computational resources. In Chapter 3, we cover the critical computational advancements introduced in WarpNL that make it efficient in a modern computing framework. This includes efficient feature encoding, introduction of a log-odds ratio for comparison of naive Bayes posterior estimates, description of schema for parallel and distributed naive Bayes architectures, and use of machine learning classifiers to perform outgroup sequence classification. Finally in Chapter 4, we explore a variant of the Dirichlet multinomial distribution that underlies the naive Bayes likelihood, called the beta-Liouville multinomial. We show that the beta-Liouville multinomial can be used to enhance classifier performance, and we provide mathematical proofs regarding its convergence during maximum likelihood estimation. Overall, this work explores the naive Bayes algorithm in a modern context and shows that it is competitive for genetic sequence classification.
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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.