Digital Commons Network^™

Topological And System‑Level Protein Interaction Network (Pin) Analyses To Deduce Molecular Mechanism Of Curcumin, Anupam Dhasmana, Swati Uniyal, Anukriti -, Vivek Kumar Kashyap, Pallavi Somvanshi, Meenu Gupta, Uma Bhardwaj, Meena Jaggi, Murali M. Yallapu, Shafiul Haque, Subhash C. Chauhan

School of Medicine Publications

Curcumin is an important bioactive component of turmeric and also one of the important natural products, which has been investigated extensively. The precise mode of action of curcumin and its impact on system level protein networks are still not well studied. To identify the curcumin governed regulatory action on protein interaction network (PIN), an interectome was created based on 788 key proteins, extracted from PubMed literatures, and constructed by using STRING and Cytoscape programs. The PIN rewired by curcumin was a scale-free, extremely linked biological system. MCODE plug-in was used for sub-modulization analysis, wherein we identified 25 modules; ClueGo plug-in …

An Unusual Case Of Campylobacter Jejuni Gastroenteritis Presenting With Acute Reversible Encephalopathy In An Immunocompetent Host, Irma Huayanay, Leonardo Pozo, Salman Bangash, Denisse Ramirez, Luis Rosas, Renzo Arauco Brown

School of Medicine Publications

Campylobacter jejuni gastroenteritis is the most frequent organism associated with acute infectious diarrhea worldwide. (e clinical presentation involves fever, diarrhea, rigors, and myalgias. Other extraintestinal symptoms that have been described involve delirium and other neurological complications, and the most well-known is Guillain-Barr´e, where there is cross-reactivity between the gastrointestinal tract and the brain. Despite previously described multiple neurological complications, there is a lack of clinical data on the association of Campylobacter-related gastroenteritis with acute encephalopathy in immunocompetent patients. (e type of population, immunocompetent stage, and unfamiliarity with the clinical presentation makes this a challenging diagnosis for clinicians. We report a …

Vertical Transmission And Venereal Transmission Of Zika Virus In A Population Of South Texas Aedes Aegypti, Jeremy Marshall

Theses and Dissertations

Zika virus has become a greater global public health concern from the occurrence of outbreaks in 2007 and its expansion to the Americas in 2015. The presence of Aedes aegypti in the Lower Rio Grande Valley and evidence of local transmission of Zika in Brownsville, Texas provides a need to research transmission dynamics of local populations. In these experiments, a locally acquired, laboratory colony of Aedes aegypti mosquitoes were infected with a blood meal featuring a Mexican isolate of Zika virus to display vector competency, vertical transmission, venereal transmission. Here, we infected 39 females, with 34 of them displaying evidence …

Emerging Agents For The Treatment Of Chagas Disease: What Is In The Preclinical And Clinical Development Pipeline?, Nieves Martínez-Peinado, Nuria Cortes-Serra, Irene Losada-Galvan, Julio A. Urbina, Ana Rodríguez, John L. Vandeberg, Maria-Jesus Pinazo, Joaquim Gascon, Julio Alonso-Padilla

School of Medicine Publications

Introduction: Chagas disease treatment relies on the lengthy administration of benznidazole and/or nifurtimox, which have frequent toxicity associated. The disease, caused by the parasite Trypanosoma cruzi, is mostly diagnosed at its chronic phase when life-threatening symptomatology manifest in approximately 30% of those infected. Considering that both available drugs have variable efficacy by then, and there are over 6 million people infected, there is a pressing need to find safer, more efficacious drugs.

Areas covered: We provide an updated view of the path to achieve the aforementioned goal. From state-of-the-art in vitro and in vivo assays based on genetically engineered …

Intoxication With Endogenous Angiotensin Ii: A Covid-19 Hypothesis, Adonis Sfera, Carolina Osorio, Nyla Jafri, Eddie Lee Diaz, Jose Campo Maldonado

School of Medicine Publications

Severe acute respiratory syndrome coronavirus 2 has spread rapidly around the globe. However, despite its high pathogenicity and transmissibility, the severity of the associated disease, COVID-19, varies widely. While the prognosis is favorable in most patients, critical illness, manifested by respiratory distress, thromboembolism, shock, and multi-organ failure, has been reported in about 5% of cases. Several studies have associated poor COVID-19 outcomes with the exhaustion of natural killer cells and cytotoxic T cells, lymphopenia, and elevated serum levels of D-dimer. In this article, we propose a common pathophysiological denominator for these negative prognostic markers, endogenous, angiotensin II toxicity. We hypothesize …

Potential Effects Of Climate Change On The Geographic Distribution Of The Endangered Plant Species Manihot Walkerae, Gisel Garza, Armida Rivera, Crystian Sadel Venegas Barrera, Jose Guadalupe Martinez-Avalos, Jon Dale, Teresa Patricia Feria-Arroyo

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

Walker’s Manihot, Manihot walkerae, is an endangered plant that is endemic to the Tamaulipan thornscrub ecoregion of extreme southern Texas and northeastern Mexico. M. walkerae populations are highly fragmented and are found on both protected public lands and private property. Habitat loss and competition by invasive species are the most detrimental threats for M. walkerae; however, the effect of climate change on M. walkerae’s geographic distribution remains unexplored and could result in further range restrictions. Our objectives are to evaluate the potential effects of climate change on the distribution of M. walkerae and assess the usefulness of natural protected areas …

Detection And Enumeration Of Bacterial Pathogens In The American Oyster (Crassostrea Virginica), Mohammad Maruf Billah

Theses and Dissertations

American oyster (Crassostrea virginica) is a popular seafood for its delicacy and high nutritional value. Based on increasing concern about contamination of bacterial pathogens in raw oyster, my research objectives have been focused on detection and enumeration of two important bacterial pathogens, Escherichia coli and Salmonella spp. in the American oyster in south Texas waters, local markets and controlled laboratory studies. Immunohistochemical and RT-PCR analyses showed substantial bacterial pathogen’s presence in gills and digestive glands of oysters collected from San Martin Lake and South Padre Island as well as local markets. Laboratory studies showed increasing trend of both …

Dialysis Access Steals And Leads To Limb Ischemia, Supraja Thunuguntla, Mohammed Rizwan, Jose E. Campo Maldonado

School of Medicine Publications

Dialysis Access Associated Steal Syndrome (DASS) reported incidence is low, (6.2%) [1]. Symptoms are dialysis induced hand pain, coldness, numbness, sensory loss which can lead to inevitable digital gangrene and amputation if the diagnosis is delayed. Duplex arterial ultrasound and electromyography (EMG) can help differentiate DASS from Ischemic monomelic neuropathy (IMN), a variation of DASS. Treatment options are individualized based on the location of the AV fistula, severity of presentation, presence of anatomical anomalies of involved vasculature. Comprehensive review of literature demonstrates this outcome of finger gangrene in young patients with ESRD is primarily associated with preexisting diffuse vascular disease …

Covid-19, Wall Building, And The Effects On Migrant Protection Protocols By The Trump Administration: The Spectacle Of The Worsening Human Rights Disaster On The Mexico-U.S. Border, Terence Garrett

Political Science Faculty Publications

The COVID-19 pandemic has repercussions well beyond the confines of borders. National border policies can thwart international efforts to combat the spread of infectious diseases. These problems are especially relevant for the United States with the spectacle of President Trump’s “big, beautiful border wall” used as leverage to maintain political and economic power domestically and globally while confronting the coronavirus pandemic. The focus of this paper is the implementation of Trump’s Zero Tolerance Policy, Migrant Protection Protocols, and the Asylum Cooperation Agreement, all aimed primarily at migrants and refugees from Central America to prevent entrance into the U.S. using the …

Analysis Of The Healthcare Mers-Cov Outbreak In King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June–August 2015 Using A Seir Ward Transmission Model, Tamer Oraby, Michael G. Tyshenko, Hanan H. Balkhy, Yasar Tasnif, Adriana Quiroz-Gaspar, Zeinab Mohamed, Ayesha Araya, Susie Elsaadany, Eman Al-Mazroa, Mohammed A. Alhelail, Yaseen M. Arabi, Mustafa Al-Zoughool

School of Mathematical & Statistical Sciences Faculty Publications

Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that has a tendency to cause significant healthcare outbreaks among patients with serious comorbidities. We analyzed hospital data from the MERS-CoV outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June–August 2015 using the susceptible-exposed-infectious-recovered (SEIR) ward transmission model. The SEIR compartmental model considers several areas within the hospital where transmission occurred. We use a system of ordinary differential equations that incorporates the following units: emergency department (ED), out-patient clinic, intensive care unit, and hospital wards, where each area has its own carrying capacity and distinguishes the transmission by …

Glutaminyl-Trna Synthetase From Pseudomonas Aeruginosa: Characterization, Structure, And Development As A Screening Platform, Yaritza Escamilla, Casey A. Hughes, Jan Abendroth, David M. Dranow, Samantha Balboa, Frank B. Dean, James M. Bullard

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

Pseudomonas aeruginosa has a high potential for developing resistance to multiple antibiotics. The gene (glnS) encoding glutaminyl-tRNA synthetase (GlnRS) from P. aeruginosa was cloned and the resulting protein characterized. GlnRS was kinetically evaluated and the KM and kcatobs , governing interactions with tRNA, were 1.0 μM and 0.15 s-1 , respectively. The crystal structure of the α2 form of P. aeruginosa GlnRS was solved to 1.9 Å resolution. The amino acid sequence and structure of P. aeruginosa GlnRS were analyzed and compared to that of GlnRS from Escherichia coli. Amino acids that interact with ATP, glutamine, and tRNA are well …

The Genetic Architecture Of The Human Cerebral Cortex, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucia Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Marcio A. Almeida, Joanne E. Curran, John Blangero

School of Medicine Publications

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area …

Integer Versus Fractional Order Seir Deterministic And Stochastic Models Of Measles, Md Rafiul Islam, Angela Peace, Daniel Medina, Tamer Oraby

School of Mathematical & Statistical Sciences Faculty Publications

In this paper, we compare the performance between systems of ordinary and (Caputo) fractional differential equations depicting the susceptible-exposed-infectious-recovered (SEIR) models of diseases. In order to understand the origins of both approaches as mean-field approximations of integer and fractional stochastic processes, we introduce the fractional differential equations (FDEs) as approximations of some type of fractional nonlinear birth and death processes. Then, we examine validity of the two approaches against empirical courses of epidemics; we fit both of them to case counts of three measles epidemics that occurred during the pre-vaccination era in three different locations. While ordinary differential equations (ODEs) …

The Infectious Headache- A Case Of Neurocysticercosis, Supraja Thunuguntla, Obinna Echeruo, Jose Campo Maldonado

School of Medicine Publications

A 50-year-old Hispanic female presented to her primary care physician with a progressively worsening headache over a week, associated with visual disturbances, prosopagnosia and episodes of disorientation. Outpatient workup with head CT showed abnormality in the ventral aspect of the left thalamus showing 1.2 × 1 cm low density cyst with approximately 2-3 mm right-left midline shift locally. Left basal ganglia showed multiple well-defined foci of low density measuring up to 3 mm reflecting edema. On admission, pertinent physical exam findings were left sided nystagmus, positive deep tendon reflexes (DTRs) in the right lower extremity (RLE), positive Babinski on the …

Detecting Invasive Fungal Disease In Surgical Patients: Utility Of The (1 3)- B-D-Glucan Assay, Jeffrey Skubic, Sharven Taghavi, Manuel Castillo-Angeles, Ramsis Ramsis, Ali Salim, Reza Askari

School of Medicine Publications

Background: The specificity and sensitivity of the (1 3)-b-d-glucan (BDG) assay in surgical patients needs further investigation. We hypothesized that the BDG assay would have lower sensitivity/specificity compared with that of medical patients.

Methods: We reviewed patients who had undergone laparotomy, gastrectomy, hepatectomy, or colectomy and had a BDG assay post-operatively.

Results: A total of 71 patients met study criteria. There were 29 (40.8%) who had proven/probable invasive fungal infection. Sensitivity for BDG level ‡80 diagnosed within one week of the assay draw was 77.3% (95% confidence interval [CI], 54.6–92.2%), and specificity was 44.9% (95% CI, 30.7–59.8). The positive predictive …

Medicina Tropical Y Su Proyeccion Actual: Un Breve Panorama [A Brief Overview: Tropical Medicine And Its Current Projection], Nathalie Chacon, Luis Alfonso Colmenares Suárez

Physician Assistant Studies Faculty Publications

La rica tradición histórica y los importantes avances científicos de la Medicina Tropical (MT) han contribuido a su inmensa proyección actual. La literatura consultada así lo refleja. Esta investigación documental apuntó a esa misma dirección y buscó enriquecer el acervo bibliográfico al respecto. Mediante la lectura crítica de referencias y el método cualitativo de Huberman y Miles se estructuró una argumentación discursiva referente a la proyección actual de la MT a lo largo de las tres secciones de este trabajo: su origen histórico, su ulterior desarrollo, sus tendencias y perspectivas futuras. El médico escocés Patrick Manson (1844-1922), es considerado como …

Hiv-Associated Neurocognitive Disorder (Hand) Biomarker Identification: Significance Analysis Of Microarrays And Two Persuasive Approaches With Random Forest, Hansapani Rodrigo, Bryan Martinez, Roberto De La Garza, Upal Roy

School of Mathematical & Statistical Sciences Faculty Publications

Background: HIV Associated Neurological Disorders (HAND) is relatively common among people with HIV-1 infection, even those taking combined antiretroviral treatment (cART). Genome-wide screening of transcription regulation in brain tissue helps in identifying substantial abnormalities present in patients’ gene transcripts and to discover possible biomarkers for HAND. This study explores the possibility of identifying differentially expressed (DE) genes, which can serve as potential biomarkers to detect HAND. In this study, we have investigated the gene expression levels of three subject groups with different impairment levels of HAND along with a control group in three distinct brain sectors: white matter, frontal cortex, …

A Tale Of Two Cities: Aedes Mosquito Surveillance Across The Texas-Mexico Border, Teresa Patricia Feria-Arroyo, Consuelo Aguilar, Cuauhtémoc Quintero Vazquez, Rene Santos-Luna, Susana Roman-Perez, Tamer Oraby, Gustavo Sanchez Tejeda, Fabian Correa Morales, Víctor M. Salazar Bueyes, Pascual Camacho Guevara

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

Cross border situations complicate epidemiologic risk assessments in transboundary regions such as the US-Mexico border. Countries have different health policies, mosquito control policies, and mosquito surveillance systems. We established a binational Aedes mosquito surveillance program in Reynosa, Tamaulipas, and McAllen, Texas by replicating a part of the Mexican Integrated Vector Monitoring System (IVMS) across the international border. The entomologic surveillance of the IVMSs is based on ova collection cups (ovitraps) and for the binational project, the surveillance protocol was modified to include an Autocidal Gravid Ovitrap (AGO) in the center of every city-block (100 m2) distribution of four ovitraps. We …

Hypothetical Human Immune Genome Complex Gradient May Help To Explain The Congenital Zika Symdrome Catastrophe In Brazil: A New Theory, F. R. S. Oliveira, C. C. Bresani-Salvi, C. N. L. Morais, A. W. Bigham, U. Braga-Neto, Gladys E. Maestre, John L. Vandeberg, E. T. A. Marques, B. Acioli-Santos

School of Medicine Publications

There are few data considering human genetics as an important risk factor for birth abnormalities related to ZIKV infection during pregnancy, even though sub-Saharan African populations are apparently more resistant to CZS as compared to populations in the Americas. We hypothesized that single nucleotide variants (SNVs), especially in innate immune genes, could make some populations more susceptible to Zika congenital complications than others. Differences in the SNV frequencies among continental populations provide great potential for Machine Learning techniques. We explored a key immune genomic gradient between individuals from Africa, Asia and Latin America, working with complex signatures, using 297 SNVs. …

Use Of >100,000 Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium Whole Genome Sequences Improves Imputation Quality And Detection Of Rare Variant Associations In Admixed African And Hispanic/Latino Populations, Madeline H. Kowalski, Huijun Qian, Ziyi Hou, Jonathan D. Rosen, Amanda L. Tapia, Yue Shan, Deepti Jain, Maria Argos, John Blangero, Juan M. Peralta

School of Medicine Publications

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation …

Non-Invasive Methods For Measuring And Monitoring Stress Physiology In Imperiled Amphibians, Edward J. Narayan, Zachery R. Forsburg, Drew R. Davis, Caitlin R. Gabor

School of Earth, Environmental, & Marine Sciences Faculty Publications

Global climate change is negatively impacting global biodiversity and ectothermic vertebrates, with amphibians being the most imperiled vertebrate taxa. Increased mean global atmospheric temperatures, high rates of habitat degradation, and exposure to infectious diseases, such as chytridiomycosis, have contributed to population declines and extinctions of rare and endangered amphibian species. Field-based monitoring of physiological endocrine traits can help determine the sub-lethal effects of environmental stressors and provide early alerts when populations are chronically stressed. Recent advances in amphibian stress endocrinology include the development and use of non-invasive methods to quantify the glucocorticoid, or stress biomarker, corticosterone. Non-invasive methods, such as …

Syndemics: Considerations For Interdisciplinary Research, Rosalynn A. Vega

Anthropology Faculty Publications

In this short piece, I explore how medical anthropology could be deployed through interdisciplinary collaborations in a way that is both theoretically rich and poised to positively impact health outcomes. In particular, I consider how research agendas focused on improving health care outcomes reveal certain limitations and underlying assumptions within the discipline. What types of methodological shifts might occur if we interrogate those limitations and assumptions? What are some alternatives? To answer these questions, I turn to the concept of “syndemics” as one example of how a human rights approach can transform the way we do anthropology for the betterment …

Regulatory Mechanisms Mediated By Peroxisome Proliferator-Activated Receptor-Β/Δ (Pparβ/Δ) In Skin Cancer, Jeffrey M. Peters, Dae Joon Kim, Moses T. Bility, Michael G. Borland, Bokai Zhu, Frank J. Gonzalez

School of Medicine Publications

Considerable progress has been made during the past twenty years towards elucidating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in skin cancer. In 1999, the original notion that PPARβ/δ was involved with epithelial cell function was postulated based on a correlation between PPARβ/δ expression and the induction of mRNAs encoding proteins that mediate terminal differentiation in keratinocytes. Subsequent studies definitively revealed that PPARβ/δ could induce terminal differentiation and inhibit proliferation of keratinocytes. Molecular mechanisms have since been discovered to explain how this nuclear receptor can be targeted for preventing and treating skin cancer. This includes the regulation of terminal differentiation, …

Prevalence And Distribution Of Ranavirus In Amphibians From, Drew R. Davis, Jillian K. Farkas, Taylor R. Kruisselbrink, Jessa L. Watters, Elyse D. Ellsworth, Jacob L. Kerby, Cameron D. Siler

School of Earth, Environmental, & Marine Sciences Faculty Publications

Several infectious diseases are threatening amphibian species worldwide and have resulted in massmortality events across the globe. An emerging group of viral pathogens (ranaviruses) are documented to cause die-offs in amphibian populations worldwide, including in several regions of the U.S. Unfortunately, large gaps remain in our understanding of the distribution of this systemic pathogen in the U.S., including within the state of Oklahoma. To address this gap in our understanding, we carried out surveys of this infectious pathogen across 14 sites in seven southeastern Oklahoma counties in spring 2015, screening 17 amphibian species from this region. Using liver and tail …

Temperature Influence On Insecticide Resistance In Aedes Aegypti And Aedes Albopictus Mosquitoes From South Texas, Wendy Soledad Salinas

Theses and Dissertations

Aedes aegypti and Aedes albopictus are vectors for several emerging arboviruses including Zika, chikungunya and dengue. Both mosquitoes are found along the Rio Grande River in South Texas, along the border between Mexico and the United States of America. These mosquito species typically reside near human settlements. A preventative measure public health official use to help halt the spread of diseases is by controlling vector population with the use of insecticides, but as temperature vary, and with the constant exposure to commonly used insecticides, mosquitoes from South Texas may be developing a resistance to the insecticides. Resistance to insecticides may …

Periodontal Pathogens Are A Risk Factor Of Oral Cavity Squamous Cell Carcinoma, Independent Of Tobacco And Alcohol And Human Papillomavirus, Ian Ganly, Liying Yang, Rachel Giese, Yuhan Hao, Carlos W. Nossa, Luc G. T. Morris, Matthew Rosenthal, Jocelyn Migliacci, Dervla Kelly, Wenzhi Tseng

School of Medicine Publications

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the …

Pathogens Without Borders: Ecological Determinants Of Sexual Risk-Taking Behaviors Among International Travelers Across The Life Course, Yok-Fong Paat, Luis R. Torres-Hostos

School of Social Work Faculty Publications

Purpose

Drawing insights from the ecological theory, the purpose of this paper is to explore social determinants related to pathways to high-risk sexual behaviors of international travelers across their life span.

Design/methodology/approach

Data were collected from 45 international travelers in Houston, a critical transit point frequented by international visitors.

Findings

Overall, several ecological settings (individuals, interpersonal, institutional and contextual) related to two typologies of international travelers (risk takers vs non-risk takers) and their inclination to engage in high-risk sexual practices in an international or/and local context were identified.

Research limitations/implications

This research calls for the need to assess high-risk sexual …

Growth Factors In The Human Body: A Conceptual Update, Estefania Alexandre, Debasish Bandyopadhyay

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

Growth factors are found in most of the organisms including insects, humans, plants, etc. The name ‘growth factors’ became known when the substances were active in stimulating the growth of cells and tissues. Growth factors are regulatory species (signaling molecules mainly proteins) that are generated by the body which function in binding to receptors on the cell surface and are required to stimulate the growth in living responsive cells by triggering cellular proliferation and/or cellular differentiation pathways, as well as by regulating gene transcription in the nucleus. They are quite versatile by promoting cell growth and act in a paracrine, …

Identification Of Inhibitors Of The Glutaminyl And Prolyl Trna Synthetases From Pseudomonas Aeruginosa, Yaritza Escamilla

Theses and Dissertations

Antibiotic resistance is a growing global threat and bacterial infections caused by antibiotic resistant bacteria have become increasingly difficult and expensive to treat with most current antibiotics. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen and a leading cause of nosocomial infections and is the leading cause of mortality in cystic fibrosis patients. Aminoacyl-tRNA synthetases (aaRSs) are a class of enzymes that catalyze the covalent attachment of amino acids to their cognate tRNAs during protein biosynthesis. The glutaminyl- tRNA synthetase from P. aeruginosa was over-expressed, enzymatically characterized and developed into a screening platform for the discovery of chemical compounds that inhibit …

The Development Of Screening Platforms To Identify Novel Anti-Infectives That Inhibit Protein Synthesis In Pseudomonas Aeruginosa, Casey Anne Hughes

Theses and Dissertations

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is a leading cause of nosocomial infections and is becoming increasingly antibiotic resistant. Aminoacyl-tRNA synthetases (aaRSs) catalyze the covalent attachment of amino acids to their cognate tRNAs and serve as validated targets for the development of new anti-infectives. In P. aeruginosa, the genome contains two genes (tyrS and tyrZ) which encode two distinct TyrRS enzymes. The genes encoding both P. aeruginosa TyrRS-Z and TyrRS-S were cloned, overexpressed in E. coli cells, and purified to homogeneity. Both forms of TyrRS were active in aminoacylation and were developed into screening platforms using scintillation proximity …