Matching Items (83)
Description
Bacteria are often regarded s pathogens, with deleterious impacts on the human body. However, it is known that the presence of trillions of bacteria on and in the human body impart beneficial effects on human health. Like a fingerprint, each individual’s microbiome is unique. The composition of bacteria in one person’s gut is different from the gut bacteria in another individual. Together, the human gut microbiome is a complex mix of organisms that is commonly referred to as “the second brain.� Its role in the human body goes beyond digestion and immune system function. The health of the microbiome factors into risk for illnesses as diverse as depression, obesity, bowel disorders and autism (Perlmutter et al., 2015). In context of the myriad of bacteria that live on and within the human body, the composition of bacteria in the gut may have the most significant impact on an individual’s well-being. This “superorganism� co-evolved with its host in order to provide essential and mutually beneficial functions (Ragonnaud et al., 2021).
Affecting millions of Americans, depression is one of the leading causes of the Global Burden of Disease (GBD), followed by anxiety (Gibson-Smith et al., 2018). Communication that occurs between the human brain and the gut microbiome has been found to be a major contributor towards mental health. The human gut microbiome is comprised of many microbes that can communicate with the brain through the gut-brain axis. However, factors such as stress and diets can interfere with this process, especially after increasing the permeability of the intestine (Khoshbin et al., 2020). Perturbation of the gut-brain axis has been implicated across a wide scale of neurodegenerative disorders, with respect to psychopathology (Bonaz et al., 2018). The environment of the gut, along with which species reside there, can help determine the link between gut function and disease. Therefore, it may be possible to prevent the degradation of an individual’s immune function and well-being through alteration of the gut microbiome. (abstract)
Affecting millions of Americans, depression is one of the leading causes of the Global Burden of Disease (GBD), followed by anxiety (Gibson-Smith et al., 2018). Communication that occurs between the human brain and the gut microbiome has been found to be a major contributor towards mental health. The human gut microbiome is comprised of many microbes that can communicate with the brain through the gut-brain axis. However, factors such as stress and diets can interfere with this process, especially after increasing the permeability of the intestine (Khoshbin et al., 2020). Perturbation of the gut-brain axis has been implicated across a wide scale of neurodegenerative disorders, with respect to psychopathology (Bonaz et al., 2018). The environment of the gut, along with which species reside there, can help determine the link between gut function and disease. Therefore, it may be possible to prevent the degradation of an individual’s immune function and well-being through alteration of the gut microbiome. (abstract)
ContributorsPisarczyk, Nicole (Author) / Penton, Christopher (Thesis director) / Huffman, Holly (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Pathogenic Gram-negative bacteria employ a variety of molecular mechanisms to combat host defenses. Two-component regulatory systems (TCR systems) are the most ubiquitous signal transduction systems which regulate many genes required for virulence and survival of bacteria. In this study, I analyzed different TCR systems in two clinically-relevant Gram-negative bacteria, i.e., oral pathogen Porphyromonas gingivalis and enterobacterial Escherichia coli. P. gingivalis is a major causative agent of periodontal disease as well as systemic illnesses, like cardiovascular disease. A microarray study found that the putative PorY-PorX TCR system controls the secretion and maturation of virulence factors, as well as loci involved in the PorSS secretion system, which secretes proteinases, i.e., gingipains, responsible for periodontal disease. Proteomic analysis (SILAC) was used to improve the microarray data, reverse-transcription PCR to verify the proteomic data, and primer extension assay to determine the promoter regions of specific PorX regulated loci. I was able to characterize multiple genetic loci regulated by this TCR system, many of which play an essential role in hemagglutination and host-cell adhesion, and likely contribute to virulence in this bacterium. Enteric Gram-negative bacteria must withstand many host defenses such as digestive enzymes, low pH, and antimicrobial peptides (AMPs). The CpxR-CpxA TCR system of E. coli has been extensively characterized and shown to be required for protection against AMPs. Most recently, this TCR system has been shown to up-regulate the rfe-rff operon which encodes genes involved in the production of enterobacterial common antigen (ECA), and confers protection against a variety of AMPs. In this study, I utilized primer extension and DNase I footprinting to determine how CpxR regulates the ECA operon. My findings suggest that CpxR modulates transcription by directly binding to the rfe promoter. Multiple genetic and biochemical approaches were used to demonstrate that specific TCR systems contribute to regulation of virulence factors and resistance to host defenses in P. gingivalis and E. coli, respectively. Understanding these genetic circuits provides insight into strategies for pathogenesis and resistance to host defenses in Gram negative bacterial pathogens. Finally, these data provide compelling potential molecular targets for therapeutics to treat P. gingivalis and E. coli infections.
ContributorsLeonetti, Cori (Author) / Shi, Yixin (Thesis advisor) / Stout, Valerie (Committee member) / Nickerson, Cheryl (Committee member) / Sandrin, Todd (Committee member) / Arizona State University (Publisher)
Created2013
Description
The study of bacterial resistance to antimicrobial peptides (AMPs) is a significant area of interest as these peptides have the potential to be developed into alternative drug therapies to combat microbial pathogens. AMPs represent a class of host-mediated factors that function to prevent microbial infection of their host and serve as a first line of defense. To date, over 1,000 AMPs of various natures have been predicted or experimentally characterized. Their potent bactericidal activities and broad-based target repertoire make them a promising next-generation pharmaceutical therapy to combat bacterial pathogens. It is important to understand the molecular mechanisms, both genetic and physiological, that bacteria employ to circumvent the bactericidal activities of AMPs. These understandings will allow researchers to overcome challenges posed with the development of new drug therapies; as well as identify, at a fundamental level, how bacteria are able to adapt and survive within varied host environments. Here, results are presented from the first reported large scale, systematic screen in which the Keio collection of ~4,000 Escherichia coli deletion mutants were challenged against physiologically significant AMPs to identify genes required for resistance. Less than 3% of the total number of genes on the E. coli chromosome was determined to contribute to bacterial resistance to at least one AMP analyzed in the screen. Further, the screen implicated a single cellular component (enterobacterial common antigen, ECA) and a single transporter system (twin-arginine transporter, Tat) as being required for resistance to each AMP class. Using antimicrobial resistance as a tool to identify novel genetic mechanisms, subsequent analyses were able to identify a two-component system, CpxR/CpxA, as a global regulator in bacterial resistance to AMPs. Multiple previously characterized CpxR/A members, as well as members found in this study, were identified in the screen. Notably, CpxR/A was found to transcriptionally regulate the gene cluster responsible for the biosynthesis of the ECA. Thus, a novel genetic mechanism was uncovered that directly correlates with a physiologically significant cellular component that appears to globally contribute to bacterial resistance to AMPs.
ContributorsWeatherspoon-Griffin, Natasha (Author) / Shi, Yixin (Thesis advisor) / Clark-Curtiss, Josephine (Committee member) / Misra, Rajeev (Committee member) / Nickerson, Cheryl (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2013
Description
Hepatitis C virus (HCV) is a globally prevalent infection which is a main contributor to the global burden of liver disease. Due to its ability to establish a chronic infection, and the lack of usefulness of traditional neutralizing antibody vaccine design in producing a protective immune response, a preventative vaccine has been notoriously difficult to produce. To overcome this, a vaccine using non-structural protein 3 (NS3) as a target to elicit a T cell specific immune response is thought to be a possible strategy for eliciting a protective immune response against hepatitis C infection. In this paper, a recombinant strain of measles virus (MV) that expresses HCV NS3 protein was analyzed. The replication fitness of this recombinant virus also indicates that this construct replicates at a higher rate than parental measles strain. It is also demonstrated through western blot analysis of protein expression and immunofluorescence that this recombinant virus expresses both the inserted HCV NS3 protein, as well as native measles proteins.
ContributorsWoell, Dana Marie (Author) / Reyes del Valle, Jorge (Thesis director) / Nickerson, Cheryl (Committee member) / Julik, Emily (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Clean water for drinking, food preparation, and bathing is essential for astronaut health and safety during long duration habitation of the International Space Station (ISS), including future missions to Mars. Despite stringent water treatment and recycling efforts on the ISS, it is impossible to completely prevent microbial contamination of onboard water supplies. In this work, we used a spaceflight analogue culture system to better understand how the microgravity environment can influence the pathogenesis-related characteristics of Burkholderia cepacia complex (Bcc), an opportunistic pathogen previously recovered from the ISS water system. The results of the present study suggest that there may be important differences in how this pathogen can respond and adapt to spaceflight and other low fluid shear environments encountered during their natural life cycles. Future studies are aimed at understanding the underlying mechanisms responsible for these phenotypes.
ContributorsKang, Bianca Younseon (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Critical flicker fusion thresholds (CFFTs) describe when quick amplitude modulations of a light source become undetectable as the frequency of the modulation increases and are thought to underlie a number of visual processing skills, including reading. Here, we compare the impact of two vision-training approaches, one involving contrast sensitivity training and the other directional dot-motion training, compared to an active control group trained on Sudoku. The three training paradigms were compared on their effectiveness for altering CFFT. Directional dot-motion and contrast sensitivity training resulted in significant improvement in CFFT, while the Sudoku group did not yield significant improvement. This finding indicates that dot-motion and contrast sensitivity training similarly transfer to effect changes in CFFT. The results, combined with prior research linking CFFT to high-order cognitive processes such as reading ability, and studies showing positive impact of both dot-motion and contrast sensitivity training in reading, provide a possible mechanistic link of how these different training approaches impact reading abilities.
ContributorsZhou, Tianyou (Author) / Nanez, Jose (Author) / Zimmerman, Daniel (Author) / Holloway, Steven (Author) / Seitz, Aaron (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-10-26
Description
Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.
ContributorsYahata, Noriaki (Author) / Morimoto, Jun (Author) / Hashimoto, Ryuichiro (Author) / Lisi, Giuseppe (Author) / Shibata, Kazuhisa (Author) / Kawakubo, Yuki (Author) / Kuwabara, Hitoshi (Author) / Kuroda, Miho (Author) / Yamada, Takashi (Author) / Megumi, Fukuda (Author) / Imamizu, Hiroshi (Author) / Nanez, Jose (Author) / Takahashi, Hidehiko (Author) / Okamoto, Yasumasa (Author) / Kasai, Kiyoto (Author) / Kato, Nobumasa (Author) / Sasaki, Yuka (Author) / Watanabe, Takeo (Author) / Kawato, Mitsuo (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2016-04-14
Description
Spaceflight and spaceflight analogue culture enhance the virulence and pathogenesis-related stress resistance of the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). This is an alarming finding as it suggests that astronauts may have an increased risk of infection during spaceflight. This risk is further exacerbated as multiple studies indicate that spaceflight negatively impacts aspects of the immune system. In order to ensure astronaut safety during long term missions, it is important to study the phenotypic effects of the microgravity environment on a range of medically important microbial pathogens that might be encountered by the crew. This ground-based study uses the NASA-engineered Rotating Wall Vessel (RWV) bioreactor as a spaceflight analogue culture system to grow bacteria under low fluid shear forces relative to those encountered in microgravity, and interestingly, in the intestinal tract during infection. The culture environment in the RWV is commonly referred to as low shear modeled microgravity (LSMMG). In this study, we characterized the stationary phase stress response of the enteric pathogen, Salmonella enterica serovar Enteritidis (S. Enteritidis), to LSMMG culture. We showed that LSMMG enhanced the resistance of stationary phase cultures of S. Enteritidis to acid and thermal stressors, which differed from the LSSMG stationary phase response of the closely related pathovar, S. Typhimurium. Interestingly, LSMMG increased the ability of both S. Enteritidis and S. Typhimurium to adhere to, invade into, and survive within an in vitro 3-D intestinal co-culture model containing immune cells. Our results indicate that LSMMG regulates pathogenesis-related characteristics of S. Enteritidis in ways that may present an increased health risk to astronauts during spaceflight missions.
ContributorsKoroli, Sara (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, C. Mark (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
White-nose syndrome (WNS) is a fungal infection devastating bat populations throughout eastern North America. WNS is caused by a fungus, Pseudogymnoascus destructans (Pd), that invades the skin of hibernating bats. While there are a number of treatments being researched, there is currently no effective treatment for WNS that is deployed in the field, except a few being tested on a limited scale. Bats have lowered immune function and response during hibernation, which may increase susceptibility to infection during the winter months. Antimicrobial peptides (AMPs) are a crucial component of the innate immune system and serve as barriers against infection. AMPs are constitutively expressed on skin and facilitate wound healing, stimulate other immune responses, and may also stay active on bat skin during hibernation. AMPs are expressed by all tissues, have direct killing abilities against microbes, and are a potential treatment for bats infected with Pd. In this investigation, the fungicidal activity of several readily available commercial AMPs were compared, and killing assay protocols previously investigated by Frasier and Lake were replicated to establish a control trial for use in future killing assays. Another aim of this investigation was to synthesize a bat-derived AMP for use in the killing assay. Sequences of bat-derived AMPs have been identified in bat skin samples obtained from a large geographic sampling of susceptible and resistant species. Contact was made with GenScript Inc., the company from which commercially available AMPs were purchased, to determine the characteristics of peptide sequences needed to synthesize an AMP for lab use. Based on recommendations from GenScript Inc., peptide sequences need to have a hydrophobicity of less than 50% and a sequence length of less than 50 amino acids. These criteria serve as a potential barrier because none of the known bat-derived sequences analyzed satisfy both of these requirements. The final aim of this study was to generate a conceptual model of the immune response molecules activated when bats are exposed to a fungal pathogen such as Pd. Overall, this work investigated sources of variability between trials of the killing assay, analyzed known bat-derived peptide sequences, and generated a conceptual model that will serve as a guideline for identification of immune response molecules on the skin of bats in future proteomics work.
ContributorsBarton, Madisen L (Author) / Moore, Marianne (Thesis director) / Penton, Christopher (Committee member) / College of Integrative Sciences and Arts (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The International Space Station (ISS) utilizes recycled water for consumption, cleaning and air humidity control. The Environmental Control and Life Support Systems (ECLSS) have been rigorously tested at the NASA Johnson Space Center. Despite the advanced engineering of the water recovery system, bacterial biofilms have been recovered from this potable water source. Microbial contamination of potable water poses a potential threat to crew members onboard the ISS. Because astronauts have been found to have compromised immune systems, bacterial strains that would not typically be considered a danger must be carefully studied to better understand the mechanisms enabling their survival, including polymicrobial interactions. The need for a more thorough understanding of the effect of spaceflight environment on polymicrobial interactions and potential impact on crew health and vehicle integrity is heightened since 1) several potential pathogens have been isolated from the ISS potable water system, 2) spaceflight has been shown to induce unexpected alterations in microbial responses, and 3) emergent phenotypes are often observed when multiple bacterial species are co- cultured together, as compared to pure cultures of single species. In order to address these concerns, suitable growth media are required that will not only support the isolation of these microbes but also the ability to distinguish between them when grown as mixed cultures. In this study, selective and/or differential media were developed for bacterial isolates collected from the ISS potable water supply. In addition to facilitating discrimination between bacteria, the ideal media for each strain was intended to have a 100% recovery rate compared to traditional R2A media. Antibiotic and reagent susceptibility and resistance tests were conducted for the purpose of developing each individual medium. To study a wide range of targets, 12 antibiotics were selected from seven major classes, including penicillin, cephalosporins, fluoroquinolones, aminoglycosides, glycopeptides/lipoglycopeptides, macrolides/lincosamides/streptogramins, tetracyclines, in addition to seven unclassified antibiotics and three reagents. Once developed, medium efficacy was determined by means of growth curve experiments. The development of these media is a critical step for further research into the mechanisms utilized by these strains to survive the harsh conditions of the ISS water system. Furthermore, with an understanding of the complex nature of these polymicrobial communities, specific contamination targeting and control can be conducted to reduce the risk to crew members. Understanding these microbial species and their susceptibilities has potential application for future NASA human explorations, including those to Mars.
ContributorsKing, Olivia Grace (Author) / Nickerson, Cheryl (Thesis director) / Barrila, Jennifer (Committee member) / Ott, Mark (Committee member) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12