Immunology and Infectious Disease | Open Access Articles

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

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Extended-Spectrum Antiprotozoal Bumped Kinase Inhibitors: A Review, Wesley C. Van Voorhis, J. Stone Doggett, Marilyn Parsons, Matthew A. Hulverson, Ryan Choi, Samuel L. M. Arnold, Michael W. Riggs, Andrew Hemphill, Daniel K. Howe, Robert H. Mealey, Audrey O. T. Lau, Ethan A. Merritt, Dustin J. Maly, Erkang Fan, Kayode K. Ojo

Veterinary Science Faculty Publications

Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites’ survival and proliferation. In this review, we review efficacy against the kinase target, the parasite growth in vitro, and in animal infection models, as well …

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Role Of Intracellular Growth During The Gastrointestinal Stage Of Listeria Monocytogenes Infection, Grant Steven Jones

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Listeria monocytogenes is a facultative intracellular bacterium that causes foodborne disease in humans. L. monocytogenes invade the gut mucosa and then disseminate, causing systemic infections associated with high mortality rates in immunocompromised individuals. It is unknown how L. monocytogenes traffic to the mesenteric lymph nodes, which represent an important bottleneck for systemic spread. In addition, little is known about the gastrointestinal stage of infection due to the general resistance of mice to oral infection with L. monocytogenes. Our laboratory developed a novel foodborne mouse model of listeriosis utilizing a murinized strain of L. monocytogenes to investigate the gastrointestinal stage …

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Immune Evasion By Division Of Labor: The Trophic Life Cycle Stage Of Pneumocystis Murina Suppresses Innate Immunity To This Opportunistic, Fungal Pathogen, Heather M. Evans

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts, including AIDS patients. Pneumocystis species have a biphasic life cycle consisting of single-nucleated trophic forms and ascus-like cysts. Both stages live within the host, and, thus, must contend with threats from the host immune system. The cyst cell wall β-glucans have been shown to stimulate immune responses in lung epithelial cells, dendritic cells and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with immune cells. In this study, the immune response to the life cycle …

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Local Admixture Of Amplified And Diversified Secreted Pathogenesis Determinants Shapes Mosaic Toxoplasma Gondii Genomes, Hernan Lorenzi, Asis Khan, Michael S. Behnke, Sivaranjani Namasivayam, Lakshmipuram S. Swapna, Michalis Hadjithomas, Svetlana Karamycheva, Deborah Pinney, Brian P. Brunk, James W. Ajioka, Daniel Ajzenberg, John C. Boothroyd, Jon P. Boyle, Marie L. Dardé, Maria A. Diaz-Miranda, Jitender P. Dubey, Heather M. Fritz, Solange M. Gennari, Brian D. Gregory, Kami Kim, Jeroen P. J. Saeij, Chunlei Su, Michael W. White, Xing-Quan Zhu, Daniel K. Howe, Benjamin M. Rosenthal, Michael E. Grigg, John Parkinson, Liang Liu, Jessica C. Kissinger

Veterinary Science Faculty Publications

Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure …

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Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Vaccines and anthelmintics induce an inflammatory response in equids. Since they are commonly given concurrently, it is practical to study any interaction between them. This study evaluated whether IVM and PYR would modulate the acute phase inflammatory response, the systemic gene expression of pro-inflammatory cytokines, and vaccine-specific titers induced by WNV, EHV, and KLH vaccines. Naturally-infected, yearling ponies were sorted by gender, then fecal epgs. They were randomly assigned to three treatment groups: IVM, PYR, and control. All ponies received vaccinations intramuscularly on days 0 and 29. Whole blood, serum, and plasma samples were collected 1, 3, and 14 days …

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Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Influenza virus is one of the major respiratory pathogens of humans as well as animals, including equines. There is an increasing evidence that bacterial infections are the most common cause of the death during influenza. In horses also, secondary bacterial pneumonia can lead to death, and surviving horses may take up to six months for the complete recovery resulting in heavy economic loss to the equine industry. Interleukin (IL)-23 mediated innate immune response has been shown to protect the host from various respiratory bacterial infections. However, studies to investigate the role of host and viral factors in the regulation of …

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Equine Serum Antibody Responses To Streptococcus Equi And Streptococcus Zooepidemicus, Rafaela De Negri

Theses and Dissertations--Veterinary Science

Streptococcus zooepidemicus (Sz) and Streptococcus equi (Se) share 98% DNA sequence homology, but display different pathogenic properties. Infection by one organism does not cross-protect against the other. To better understand pathogenic differences between these organisms and gain information about which proteins are expressed in horses infected experimentally with Se, intrauterine Sz or naturally with respiratory Sz we compared antibody specificities of convalescent sera using ELISA. These comparisons were based on sets of 8 and 14 immunoreactive recombinant proteins of Se strain CF32 and Sz strain NC78, respectively. Sera from donkeys that were previously naturally affected with strangles and later developed …

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Evidence For The Maturation Of Cellular Immune Responses In Equine Infectious Anemia Virus-Infected Ponies, Chong Liu

Theses and Dissertations--Veterinary Science

Equine infectious anemia virus (EIAV) has been used as a model to investigate protective mechanisms against lentiviruses. Unlike other lentiviruses, EIAV replication can be eventually controlled in most infected horses leading to an inapparent carrier state free of overt clinical signs which can last for many years. Maintenance of this carrier state is absolutely dependent on active immune responses as evidenced by the fact that immunosuppressive drugs can induce the recurrence of disease. However, the immune mechanisms that are responsible for this control of infection are not yet identified. As the resolution of the initial infection is correlated with the …

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Rhodococcus Equi Infection And Interferon-Gamma Regulation In Foals, Lingshuang Sun

Theses and Dissertations--Veterinary Science

Rhodococcus equi (R. equi) is one of the most serious causes of pneumonia in young foals. The clinical disease is of great concern to breeding farms worldwide due to the impact of mortality on economic losses. While adult horses are resistant to R. equi, foals exhibit a distinct age-associated susceptibility. The mechanism underlying this susceptibility in foals is not well understood. Interferon-gamma (IFNg) plays an important role in the clearance of R. equi, but its expression is impaired in neonatal foals. Moreover, the regulation of this age-related IFNg expression in foals remains unknown. In humans, IFNg …

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Optimizing Qpcr For The Quantification Of Periodontal Pathogens In A Complex Plaque Biofilm, Sreenatha S. Kirakodu, M. Govindaswami, Michael John Novak, Jeffrey L. Ebersole, Karen F. Novak

Center for Oral Health Research Faculty Publications

Quantitative PCR (qPCR) has recently been used to quantify microorganisms in complex communities, including dental plaque biofilms. However, there is variability in the qPCR protocols being used. This study was designed to evaluate the validity of two of these variables with the intent of developing a more standardized qPCR protocol. The two variables evaluated were (1) the use of DNA content versus actual cell counts to estimate bacterial numbers in mixed plaque samples and (2) the effectiveness of three different universal primers versus species specific primers in amplifying specific target pathogens in these samples. Results lead to the development of …

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Full-Text Articles in Immunology and Infectious Disease

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Veterinary Science Faculty Publications

Role Of Intracellular Growth During The Gastrointestinal Stage Of Listeria Monocytogenes Infection, Grant Steven Jones

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Immune Evasion By Division Of Labor: The Trophic Life Cycle Stage Of Pneumocystis Murina Suppresses Innate Immunity To This Opportunistic, Fungal Pathogen, Heather M. Evans

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Veterinary Science Faculty Publications

Modulation Of Vaccine-Induced Responses By Anthelmintic Treatment In Ponies, Emily Rubinson

Theses and Dissertations--Medical Sciences

Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Equine Serum Antibody Responses To Streptococcus Equi And Streptococcus Zooepidemicus, Rafaela De Negri

Theses and Dissertations--Veterinary Science

Evidence For The Maturation Of Cellular Immune Responses In Equine Infectious Anemia Virus-Infected Ponies, Chong Liu

Theses and Dissertations--Veterinary Science

Rhodococcus Equi Infection And Interferon-Gamma Regulation In Foals, Lingshuang Sun

Theses and Dissertations--Veterinary Science

Optimizing Qpcr For The Quantification Of Periodontal Pathogens In A Complex Plaque Biofilm, Sreenatha S. Kirakodu, M. Govindaswami, Michael John Novak, Jeffrey L. Ebersole, Karen F. Novak

Center for Oral Health Research Faculty Publications