Digital Commons Network^™

Using Molecular Diagnostics To Develop Therapeutic Strategies For Carbapenem-Resistant Gram-Negative Infections, Fred C. Tenover

Biology Faculty Publications

Infections caused by multidrug-resistant Gram-negative organisms have become a global threat. Such infections can be very difficult to treat, especially when they are caused by carbapenemase-producing organisms (CPO). Since infections caused by CPO tend to have worse outcomes than non-CPO infections, it is important to identify the type of carbapenemase present in the isolate or at least the Ambler Class (i.e., A, B, or D), to optimize therapy. Many of the newer beta-lactam/beta-lactamase inhibitor combinations are not active against organisms carrying Class B metallo-enzymes, so differentiating organisms with Class A or D carbapenemases from those with Class B enzymes rapidly …

The Ghost Of Hosts Past: Impacts Of Host Extinction On Parasite Specificity, Maxwell J. Farrell, Andrew W. Park, Clayton E. Cressler, Tad Dallas, Shan Huang, Nicole Mideo, Ignacio Morales-Castilla, T. Jonathan Davies, Patrick Stephens

Faculty Publications

A growing body of research is focused on the extinction of parasite species in response to host endangerment and declines. Beyond the loss of parasite species richness, host extinction can impact apparent parasite host specificity, as measured by host richness or the phylogenetic distances among hosts. Such impacts on the distribution of parasites across the host phylogeny can have knock-on effects that may reshape the adaptation of both hosts and parasites, ultimately shifting the evolutionary landscape underlying the potential for emergence and the evolution of virulence across hosts. Here, we examine how the reshaping of host phylogenies through extinction may …

The Future Of Zoonotic Risk Prediction, Colin J. Carlson, Maxwell J. Farrell, Zoe Grange, Barbara A. Han, Nardus Mollentze, Alexandra L. Phelan, Angela L. Rasmussen, Gregory F. Albery, Bernard Bett, David M. Brett-Major, Lily E. Cohen, Tad Dallas, Evan A. Eskew, Anna C. Fagre, Kristian M. Forbes, Rory Gibb, Sam Halabi, Charlotte C. Hammer, Rebecca Katz, Jason Kindrachuk, Renata L. Muylaert, Felicia B. Nutter, Joseph Ogola, Kevin J. Olival, Michelle Rourke, Sadie J. Ryan, Noam Ross, Stephanie N. Seifert, Tarja Sironen, Claire J. Standley, Kishana Taylor, Marietjie Venter, Paul W. Webala

Faculty Publications

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open …

Phenotypic/Genotypic Profile Of Oxa-10-Like-Harboring, Carbapenem-Resistant Pseudomonas Aeruginosa: Using Validated Pharmacokinetic/Pharmacodynamic In Vivo Models To Further Evaluate Enzyme Functionality And Clinical Implications, Fred C. Tenover, Christian M. Gill, Adrian Brink, Chun Yat Chu, Jennifer Coetzee, George Dimopoulos, Clinton Moodley, Christoffel Johannes Opperman, Spyros Pournaras, Isabella A. Tickler, Hafsah Deepa Tootla, Sophia Vourli, David P. Nicolau

Biology Faculty Publications

In vitro MICs and in vivo pharmacodynamics of ceftazidime and cefepime human-simulated regimens (HSR) against modified carbapenem inactivation method (mCIM)-positive Pseudomonas aeruginosa isolates harboring different OXA-10-like subtypes were described. The murine thigh model assessed ceftazidime (2 g every 8 h [q8h] HSR) and cefepime (2 g and 1 g q8h HSR). Phenotypes were similar despite possessing OXA-10-like subtypes with differing spectra. Ceftazidime produced ≥1-log10 killing in all isolates. Cefepime activity was dose dependent and MIC driven. This approach may be useful in assessing the implications of β-lactamase variants.

Embryonic And Neonatal Mouse Cochleae Are Susceptible To Zika Virus Infection, Vidhya Munnamalai, Nabilah H. Sammudin, Caryl A. Young, Ankita Thawani, Richard J. Kuhn, Donna M. Fekete

Department of Biological Sciences Faculty Publications

Congenital Zika Syndrome (CZS) is caused by vertical transmission of Zika virus (ZIKV) to the gestating human fetus. A subset of CZS microcephalic infants present with reduced otoacoustic emissions; this test screens for hearing loss originating in the cochlea. This observation leads to the question of whether mammalian cochlear tissues are susceptible to infection by ZIKV during development. To address this question using a mouse model, the sensory cochlea was explanted at proliferative, newly post-mitotic or maturing stages. ZIKV was added for the first 24 h and organs cultured for up to 6 days to allow for cell differentiation. Results …

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Dna-Encoded Chemistry Technology Yields Expedient Access To Sars-Cov-2m Pro Inhibitors, Srinivas Chamakuri, Shuo Lu, Melek Nihan Ucisik, Kurt M Bohren, Ying-Chu Chen, Huang-Chi Du, John C Faver, Ravikumar Jimmidi, Feng Li, Jian-Yuan Li, Pranavanand Nyshadham, Stephen S Palmer, Jeroen Pollet, Xuan Qin, Shannon E Ronca, Banumathi Sankaran, Kiran L Sharma, Zhi Tan, Leroy Versteeg, Zhifeng Yu, Martin M Matzuk, Timothy Palzkill, Damian W Young

Faculty, Staff and Students Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed more than 4 million humans globally, but there is no bona fide Food and Drug Administration–approved drug-like molecule to impede the COVID-19 pandemic. The sluggish pace of traditional therapeutic discovery is poorly suited to producing targeted treatments against rapidly evolving viruses. Here, we used an affinity-based screen of 4 billion DNA-encoded molecules en masse to identify a potent class of virus-specific inhibitors of the SARS-CoV-2 main protease (Mpro) without extensive and time-consuming medicinal chemistry. CDD-1714, the initial three-building-block screening hit (molecular weight [MW] = 542.5 g/mol), was a potent inhibitor (inhibition …

Cellular Activity Of Salmonella Typhimurium Artab Toxin And Its Receptor-Binding Subunit, Elise Overgaard, Brad Morris, Omid Mohammad Mousa, Adriana Rodriguez, Leyla Cufurovic, Richard S. Beard, Juliette K. Tinker

Biology Faculty Publications and Presentations

Salmonellosis is among the most reported foodborne illnesses in the United States. The Salmonella enterica Typhimurium DT104 phage type, which is associated with multidrug-resistant disease in humans and animals, possesses an ADP-ribosylating toxin called ArtAB. Full-length artAB has been found on a number of broad-host-range non-typhoidal Salmonella species and serovars. ArtAB is also homologous to many AB₅ toxins from diverse Gram-negative pathogens, including cholera toxin (CT) and pertussis toxin (PT), and may be involved in Salmonella pathogenesis, however, in vitro cellular toxicity of ArtAB has not been characterized. artAB was cloned into E. coli and initially isolated …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Antimicrobial Resistance: A Challenge Awaiting The Post-Covid-19 Era, Tekle Airgecho Lobie, Aklilu Abrham Roba, James Alexander Booth, Knut Ivan Kristiansen, Abraham Aseffa, Kirsten Skarstad, Magnar Bjørås

Research on Antimicrobial Resistance

Microbe exposure to pharmaceutical and non-pharmaceutical agents plays a role in the development of antibiotic resistance. The risks and consequences associated with extensive disinfectant use during the COVID-19 pandemic remain unclear. Some disinfectants, like sanitizers, contain genotoxic chemicals that damage microbial DNA, like phenol and hydrogen peroxide. This damage activates error-prone DNA repair enzymes, which can lead to mutations that induce antimicrobial resistance. Public health priority programs that have faced drug-resistance challenges associated with diseases, such as tuberculosis, HIV, and malaria, have given less attention to risks attributable to the COVID-19 pandemic. Pathogen-specific programs, like the directly observed treatment strategy …

Editorial Board

Karbala International Journal of Modern Science

No abstract provided.

Serological Analyses Of Human Brucellosis In Ngara And Kibondo Districts, Tanzania, Jestina V Katandukila, Yeremia J Chuhila, Fred D Chibwana

Tanzania Journal of Science

Brucellosis, a zoonotic disease transmitted by Brucella species, is transmitted to humans from infected animals through handling dairy products like milk, blood, and semen. Although some human communities in Tanzania live close to livestock, the status of human brucellosis in Ngara and Kibondo Districts in Kagera and Kigoma regions, respectively, is poorly understood. As such, the present study aimed to investigate the status of human brucellosis in north-western Tanzania, particularly Ngara and Kibondo Districts, where the risk of contracting zoonotic diseases, including brucellosis, is high due to the abundance of livestock. Among the screened sera (n = 450), the prevalence …

Evaluation Of Antibacterial Activities Of Tanzanian Moringa Oleifera Extracts Against Escherichia Coli And Klebsiella Pneumonia Clinical Isolates, Sartaz Begum, Jenipher S. Asenga, Valence M.K. Ndesendo, Baraka L. Ngingo

Tanzania Journal of Science

In vitro antibacterial activities of methanolic leaf and seed extracts of Moringa oleifera grown in Dodoma, Tanzania were evaluated using standard microdilution and disc diffusion methods against extended spectrum beta lactamase producing Gram negative bacteria (Escherichia coli and Klebsiella pneumoniae). Microdilution method showed no activity at concentration of 20 mg/mL for all the extracts except leaf extract which exhibited minimum inhibition at concentration of  2.5 µg/mL for E. Coli but when high concentrations of the extracts were used in the disc diffusion method then the results exhibited the highest killing susceptibility at concentration of 0.4 g/mL with zone of inhibition …

Understanding The Mechanistic Roles Of Integrin Alpha 6 In Tumor Development Using A Humanized Zebrafish (Danio Rerio) Model System, Ashley B. Williams

Honors College Theses

Present day cancer incidence and mortality rates indicate the need for effective cancer diagnostic tools and targeted cancer therapeutic strategies. Recent studies have focused on the biological pathways of cells and tumor microenvironments to identify putative biomarkers and potential drug targets as diagnostic and therapeutic tools. Human integrins, adhesion receptors, have become the focal points in these studies, specifically Integrin Alpha 6 (ITGA6) which has been implicated in major tumor progression roles: metastasis and angiogenesis. These characteristics make ITGA6 an excellent candidate for potential drug or diagnostic target, however, the mechanism by which ITGA6 facilitates tumor progression remains unclear. Cell …

A Comparison Of The Evolution, Structure, And Function Of Sars-Cov And Sars-Cov-2 Spike Proteins, Tai Michaels

The Yale Undergraduate Research Journal

As the COVID-19 pandemic has developed into the largest pandemic of the twenty-first century, it has become apparent that this disease, caused by the SARS-CoV-2 virus, is unlike anything the modern world has faced before. Not only has the disease infected more than 16 million people worldwide, but its rapid spread has drawn global attention to the gaps in our understanding of its pathogenesis and the development of vaccines and treatments. One of the most important topics of research in the disease is the viral spike (S) protein which facilitates binding and entering host cells and plays a key role …

The Size And Culturability Of Patient-Generated Sars-Cov-2 Aerosol, Joshua L. Santarpia, Vicki L. Herrera, Danielle N. Rivera, Shanna Ratnesar-Shumate, St. Patrick Reid, Daniel N. Ackerman, Paul Denton, Jacob W.S. Martens, Ying Fan, Nicholas Conoan, Michael V. Callahan, James V. Lawler, David M. Brett-Major, John J. Lowe

Biology Faculty Publications

Background

Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission.

Objective

We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020.

Methods

Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western …

The Immunoregulation Of Autoimmune Diabetes, Hao Hu

Arts & Sciences Graduate Student Theses and Dissertations

How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Graduate Student Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …

Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster

Arts & Sciences Graduate Student Theses and Dissertations

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …

Characterization Of Metabolic Gene Expression In The Raw 264.7 Monocyte Cell Line, Lauren Macaisa

PANDION: The Osprey Journal of Research and Ideas

Immune cells undergo changes in gene expression and metabolism when activated by a foreign molecule. Although the changes are short-lived in response to an acute infection, they persist in disorders with underlying chronic inflammation. To understand how changes in gene expression relate to changes in metabolism, the expression of metabolic transporter proteins, was analyzed in response to chronic inflammation in a mouse monocyte cell line. Specifically, Glucose Transporter-1 (GLUT1), Monocarboxylate Transporter-1 (MCT1), Monocarboxylate Transporter-4 (MCT4), and Glutamate Aspartate Transporter (GLAST) were analyzed, and it was hypothesized that all the transporters would increase in expression in response to a prolonged inflammatory …

Effects Of Covid-19 On Global Research In Stem, Michelle Hoang, Santanu De

Biology Faculty Articles

A global public health emergency like the Coronavirus Infectious Disease 2019 (COVID-19) pandemic requires accurate and timely data collection in the research community. High impact research in science, technology, engineering, and mathematics (STEM) has been prioritized in the fight against COVID-19. The present study investigated the impact of COVID-19 on STEM research and the collaboration between global research institutions and industries. It was noted that COVID-19 had caused significant delays in non-COVID-19-related research projects and the onset of several remote studies. Most importantly, researchers in the STEM fields directed their attention and expertise to help mitigate virus transmission, treat patients, …

Trem2 Is Thyroid Hormone Regulated Making The Trem2 Pathway Druggable With Ligands For Thyroid Hormone Receptor., Skylar J. Ferrara, Priya Chaudhary, Margaret J. Debell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan

Biology Faculty Publications and Presentations

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a …

Temperatures Influence Susceptibility To Insecticides In Aedes Aegypti And Aedes Albopictus (Diptera: Culicidae) Mosquitoes, Wendy S. Salinas, Teresa Patricia Feria-Arroyo, Christopher Vitek

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

Aedes aegypti and Aedes albopictus (Diptera: Culicidae) are vectors for several arboviruses, including dengue, Zika virus and chikungunya virus. The primary method of controlling these diseases is controlling the vector population, often with insecticides. Insecticide resistance may impact the success of these efforts. We tested the effect of variable temperature exposures on susceptibility to insecticides by exposing adult A. aegypti and A. albopictus to different temperatures and tested their susceptibility to insecticides. We hypothesized that adults maintained at high temperatures would show increased susceptibility to insecticides relative to lower temperatures. Colony mosquitoes were hatched, reared to adulthood and then maintained …

The Origin Of Ticks And The Genesis And Emergence Of Lyme Disease, Alan L. Gillen, Matthew Eakin

Faculty Publications and Presentations

Ticks are notorious for their capability of transmitting diseases that have debilitated humanity for thousands of years. They can confer lifelong chronic ailments via pathogenic bacterial species that they harbor inside themselves. These parasitic tick species, namely the Ixodes scapularis tick is responsible for hundreds of thousands of Lyme disease infections each year. This profound tick continues to produce the highest rate of zoonotic disease in the United States each year. Many may ask why these tick species are so infectious when ticks were originally designed by a benevolent God. Why would a good Creator choose to design a creature …

Diminishing Opportunities For Sustainability Of Coastal Cities In The Anthropocene: A Review, John W. Day, Joel D. Gunn, Joseph Robert Burger

Biology Faculty Publications

The world is urbanizing most rapidly in tropical to sub-temperate areas and in coastal zones. Climate change along with other global change forcings will diminish the opportunities for sustainability of cities, especially in coastal areas in low-income countries. Climate forcings include global temperature and heatwave increases that are expanding the equatorial tropical belt, sea-level rise, an increase in the frequency of the most intense tropical cyclones, both increases and decreases in freshwater inputs to coastal zones, and increasingly severe extreme precipitation events, droughts, freshwater shortages, heat waves, and wildfires. Current climate impacts are already strongly influencing natural and human systems. …

Parasitic Disease Surveillance, Mississippi, Usa, Richard S. Bradbury, Meredith Lane, Irene Arguello, Sukwan Handali, Gretchen Cooley, Nils Pilotte, John M. Williams, Sam Jameson, Susan P. Montgomery, Kathryn Hellmann, Michelle Tharp, Lisa Haynie, Regina Galloway, Bruce Brackin, Brian Kirmse, Lisa Stempak, Paul Byers, Steven Williams, Fazlay Faruque, Charlotte V. Hobbs

Biological Sciences: Faculty Publications

Surveillance for soil-transmitted helminths, strongyloidiasis, cryptosporidiosis, and giardiasis was conducted in Mississippi, USA. PCR performed on 224 fecal samples for all soil-transmitted helminths and on 370 samples for only Necator americanus and Strongyloides stercoralis identified 1 S. stercoralis infection. Seroprevalences were 8.8% for Toxocara, 27.4% for Cryptosporidium, 5.7% for Giardia, and 0.2% for Strongyloides parasites.

Characterizing Bacterial Communities Across A Nutrient Gradient Over Winter Months, Emily Jin Searles Stone

Theses, Dissertations and Culminating Projects

When trying to understand how anthropogenic activities affect patterns in community ecology, bacterial communities are frequently neglected. These bacterial communities are essential to the overall health and stability of several different ecosystems. As nutrient pollution increases, some bacterial taxa may increase, causing an imbalance in food web dynamics and disrupting biogeochemical cycles. Next-generation sequencing coupled with water chemistry measurements has allowed for association testing between site water characteristics and bacterial taxa. By examining bacteria along a natural nutrient gradient over winter months in Overpeck Creek in northern New Jersey, this research shows that anthropogenic activities, specifically nutrient pollution, can alter …

The Invasive Bank Vole (Myodes Glareolus): A Model System For Studying Parasites And Ecoimmunology During A Biological Invasion, Andrew Mcmanus, Celia V. Holland, Heikki Henttonen, Peter Stuart

Publications

Animals, vol. 11, no. 9. © 2021 by the authors.

In The Search For Novel Treatments For Chagas' Disease Using Cutting-Edge Imaging Technology, Karsten Dieter Amezcua Winter

Open Access Theses & Dissertations

Chagas disease (ChD) is caused by Trypanosoma cruzi (T. cruzi), an intracellular protozoan parasite. ChD has a global mortality of 15,000 annual deaths, and approximately, 8-10 million people are infected. There is growing concern in the United States as autochthonous cases of ChD have been reported in the southern region. The two available treatments are only partially effective and highly toxic. N-aroyl derivatives and α, β-unsaturated ketones have been previously tested against Leishmania, a closely related parasite, demonstrating selective toxicity towards the microorganism. The objective of this study is to evaluate a drug library consisting of 21 α, β-unsaturated ketones …

The Ecology Of Rural Roads: Effects, Management, And Research, Alisa W. Coffin, Douglas S. Ouren, Neil D. Bettez, Luís Borda-De-Água, Amy E. Daniels, Clara Grilo, Jochen A.G. Jaeger, Laetitia M. Navarro, Haiganoush K. Preisler, Emily Rauschert

Biological, Geological, and Environmental Faculty Publications

No abstract provided.