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Relationships Between Factors Influencing Biofilm Formation And Pathogen Retention In Complex Rhizosphere Microbial Communities, Aaron Coristine

Theses and Dissertations (Comprehensive)

Riparian wetlands are unique habitats facilitating all forms of life. The riverbanks of these environments provide ideal conditions for bacteria, plants, and higher organisms. Of particular interest to this research was the variation in microbial community structure at high, intermediate and poor water quality impacted areas. Assessing the capabilities of plants to retain microbial pathogens was identified. Root systems and corresponding soil are ideal locations for bacterial deposition, resulting in attachment at these areas. Biofilm production in these regions is important for long-term establishment, leading to persistence and potential naturalization. Opportunistic pathogens originating from mammalian fecal matter are introduced into …

Structure Of The Picornavirus Replication Platform: A Potential Drug Target For Inhibiting Virus Replication, Meghan Suzanne Warden

Chemistry & Biochemistry Theses & Dissertations

Picornaviruses are small, positive-stranded RNA viruses, divided into twelve different genera. Members of the Picornaviridae family cause a wide range of human and animal diseases including the common cold, poliomyelitis, foot and mouth disease, and dilated cardiomyopathy. The picornavirus genome is replicated via a highly conserved mechanism involving a presumed cloverleaf structure located at the 5’ noncoding region of the virus genome. The 5’ cloverleaf consists of three stem loops (B, C, and D) and one stem (A), which interact with a variety of virus and host cell proteins during replication. In this dissertation, human rhinovirus serotype 14 (HRV-14) SLB …

Structural Evidence Of A Major Conformational Change Triggered By Substrate Binding In Dape Enzymes: Impact On The Catalytic Mechanism, Boguslaw Nocek, Cory Reid, Anna Starus, Tahirah Heath, David Bienvenues, Jerzy Osipiuk, Robert Jedrzeczak, Andrzej Joachimiak, Daniel P. Becker Ph.D., Richard C. Holz

Chemistry: Faculty Publications and Other Works

The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to …

Lipophosphoglycan Polymorphisms Do Not Affect Leishmania Amazonensis Development In The Permissive Vectors Lutzomyia Migonei And Lutzomyia Longipalpis, Paula M. Nogueira, Agna C. Guimarães, Rafael R. Assis, Jovana Sadlova, Jitka Myskova, Katerina Pruzinova, Jana Hlavackova, Salvatore J. Turco, Ana C. Torrecilhas, Petr Volf, Rodrigo P. Soares

Molecular and Cellular Biochemistry Faculty Publications

Background: Lipophosphoglycan (LPG) is a dominant surface molecule of Leishmaniapromastigotes. Its species-specific polymorphisms are found mainly in the sugars that branch off the conserved Gal(β1,4)Man(α1)-PO₄ backbone of repeat units. Leishmania amazonensis is one of the most important species causing human cutaneous leishmaniasis in the New World. Here, we describe LPG intraspecific polymorphisms in two Le. amazonensis reference strains and their role during the development in three sand fly species.

Results: Strains isolated from Lutzomyia flaviscutellata (PH8) and from a human patient (Josefa) displayed structural polymorphism in the LPG repeat units, possessing side chains with 1 and 2 β-glucose …

Structural And Functional Insights Into The Role Of Bamd And Bame Within The Β-Barrel Assembly Machinery In Neisseria Gonorrhoeae, Aleksandra E. Sikora, Igor H. Wierzbicki, Ryszard A. Zielke, Rachael F. Ryner, Konstantin V. Korotkov, Susan K. Buchanan, Nicholas Noinaj

Molecular and Cellular Biochemistry Faculty Publications

The β-barrel assembly machinery (BAM) is a conserved multicomponent protein complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria. Given its role in the production of OMPs for survival and pathogenesis, BAM represents an attractive target for the development of therapeutic interventions, including drugs and vaccines against multidrug-resistant bacteria such as Neisseria gonorrhoeae. The first structure of BamA, the central component of BAM, was from N. gonorrhoeae, the etiological agent of the sexually transmitted disease gonorrhea. To aid in pharmaceutical targeting of BAM, we expanded our studies to BamD and BamE within …

The Pul37 Tegument Protein Guides Alphaherpesvirus Retrograde Axonal Transport To Promote Neuroinvasion, Alexsia L. Richards, Patricia J. Sollars, Jared D. Pitts, Austin M. Stults, Ekaterina E. Heldwein, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

A hallmark property of the neurotropic alpha-herpesvirinae is the dissemination of infection to sensory and autonomic ganglia of the peripheral nervous system following an initial exposure at mucosal surfaces. The peripheral ganglia serve as the latent virus reservoir and the source of recurrent infections such as cold sores (herpes simplex virus type I) and shingles (varicella zoster virus). However, the means by which these viruses routinely invade the nervous system is not fully understood. We report that an internal virion component, the pUL37 tegument protein, has a surface region that is an essential neuroinvasion effector. Mutation of this region rendered …

Human Metapneumovirus Induces Formation Of Inclusion Bodies For Efficient Genome Replication And Transcription, Nicolás P. Cifuentes-Muñoz, Jean Branttie, Kerri Beth Slaughter, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence in situ hybridization (FISH) protocol was established to detect different viral RNA …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo Delho, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent …

Type Ix Secretion System: Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated And Defective In Neuroinvasion, Arun Saravanakumar Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Ezhumalai Muthukrishnan, Sathish Kumar Natarajan, David Steffen, Hiep Vu, Gustavo A. Delhon, Fernando Osorio, Thomas M. Petro, Shi-Hua Xiang, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

ABSTRACT Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the …

Capacity Of Human Immunodeficiency Virus Targeting Chimeric Antigen Receptor T Cells To Eliminate Follicular Dendritic Cells Bearing Human Immunodeficiency Virus Immune Complexes, Matthew T. Ollerton

Theses and Dissertations

An important obstacle to a functional cure for HIV/AIDS is the persistence of viral reservoirs found throughout the body in various cells and tissues. Reservoirs can be latently infected cells, or in the case of follicular dendritic cells (FDC), non-infected cells that trap infectious virus on their surface through immune complexes (HIV-IC). Although several strategies have been employed to target and eliminate viral reservoirs, they are short-lived and ineffective. In an attempt to provide a long-term approach, chimeric antigen receptor T (CAR-T) cells were designed to eliminate native HIV on FDCs. Although effective at eliminating HIV-infected cells, and halting spreading …

Role Of Incompatibility Group 1 (Inci1) Plasmid-Encoded Factors On Salmonella Enterica Antimicrobial Resistance And Virulence, Pravin Raghunath Kaldhone

Graduate Theses and Dissertations

Foodborne illnesses are a leading cause of infectious diseases in the world. Among enteric organisms Salmonella is a key pathogen. It’s high prevalence in poultry and other food-animal sources make it imperative to study. Salmonella has the ability to modify its genetic content with help of mobile genetic elements such as plasmids. Incompatibiltiy group 1 (IncI1) plasmids are commonly reported in Salmonella. This study evaluates role on IncI1 plasmids in antimicrobial resistance and virulence in Salmonella. Genetic determinants of resistance and virulence are noted among our IncI1-containing Salmonella isolates. These genetic elements are also transferable and reported to carry respective …

Mechanism Elucidation And Inhibitor Discovery Against Serine And Metallo-Beta-Lactamases Involved In Bacterial Antibiotic Resistance, Orville A. Pemberton

USF Tampa Graduate Theses and Dissertations

The emergence and proliferation of Gram-negative bacteria expressing β-lactamases is a significant threat to human health. β-Lactamases are enzymes that degrade the β-lactam antibiotics (e.g., penicillins, cephalosporins, monobactams, and carbapenems) that we use to treat a diverse range of bacterial infections. Specifically, β-lactamases catalyze a hydrolysis reaction where the β-lactam ring common to all β-lactam antibiotics and responsible for their antibacterial activity, is opened, leaving an inactive drug. There are two groups of β-lactamases: serine enzymes that use an active site serine residue for β-lactam hydrolysis and metalloenzymes that use either one or two zinc ions for catalysis. Serine enzymes …

Effectiveness Of Composting As A Biosecure Disposal Method For Porcine Epidemic Diarrhea Virus (Pedv)-Infected Pig Carcasses, Sarah Vitosh-Sillman, John Dustin Loy, Bruce Brodersen, Clayton Kelling, Kent M. Eskridge, Amy Millmier Schmidt

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine epidemic diarrhea virus (PEDV) is an enteric disease of swine that has emerged as a worldwide threat to swine herd health and production. Substantial research has been conducted to assess viability of the virus on surfaces of vehicles and equipment, in feed and water, and on production building surfaces, but little is known about the persistence in PEDV-infected carcasses and effective disposal methods thereof. This study was conducted to quantify the persistence of PEDV RNA via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) at various time-temperature combinations and in infected piglet carcasses subjected to composting. Although this method …

High-Throughput Single-Molecule Telomere Characterization, Jennifer Mccaffrey, Eleanor Young, Katy Lassahn, Justin Sibert, Steven Pastor, Harold Riethman, Ming Xiao

School of Medical Diagnostics & Translational Sciences Publications

We have developed a novel method that enables global subtelomere and haplotype-resolved analysis of telomere lengths at the single-molecule level. An in vitro CRISPR/Cas9 RNA-directed nickase system directs the specific labeling of human (TTAGGG) n DNA tracts in genomes that have also been barcoded using a separate nickase enzyme that recognizes a 7bp motif genome-wide. High-throughput imaging and analysis of large DNA single molecules from genomes labeled in this fashion using a nanochannel array system permits mapping through subtelomere repeat element (SRE) regions to unique chromosomal DNA while simultaneously measuring the (TTAGGG) n tract length at the end of each …

Kinetic Characterization Of Listeria Monocytogenes 2-C- Methyl-D-Erythritol 4-Phosphate Cytidylyltransferase ( Cms ) Enzymes Using High Performance Liquid Chromatography ( Hplc ), Mark Oblazny

Theses and Dissertations

Infectious diseases, with increasing prevalence of antibiotic resistant bacteria, coupled with the declining rate in discovery of antimicrobial agents, impose one of the most significant threats to human health. Here we identify 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (CMS) as a valid target for antibiotic development which is an enzyme in pathogenic organisms that leads to the biosynthesis of isoprene precursor molecules. Isoprene molecules are one of nature’s most common building blocks that are vital to many biological metabolic processes and are synthesized via the mevalonic acid dependent (MVA), or methylerythritol phosphate (MEP) pathway. Vertebrates utilize the MVA pathway, while many pathogenic bacteria …

The Biochemical Assessment Of Two Secreted Acid Phosphatases From Leishmania Tarentolae, Their Response To Electric Fields, Glycosidase Incubation, And / Or Vanadium, Benjamin M. Dorsey

Theses and Dissertations

Leishmaniasis, as defined by the Center for Disease Control and Prevention, is a neglected tropical disease with 1.6 million new cases reported each year. However, there is yet to be safe, effective, and affordable treatments provided to those affected by this disease1. Still underappreciated as a potential pharmaceutical targets, especially for cutaneous leishmaniasis infections, are the two isozymes of secreted acid phosphatase (SAP); secreted acid phosphatase 1 (SAP1) and secreted acid phosphatase 2 (SAP2). These enzymes are involved in the survival of the parasite in the sand fly vector, and the prevention of host macrophages from forming parasitophorous vacuole and …

Effects Of Carboxylated Nanodiamonds On Macrophages During And After Differentiation, Maisoun E. Bani Hani

Biological Sciences Theses & Dissertations

Nanodiamonds (ND) are a carbon-based nanomaterial that are increasingly being proposed for developing novel imaging techniques, as carriers of biomolecules and therapeutic drugs, as coatings for implants, and for other biomedical applications. The exceptional chemical, mechanical, and optical properties of ND make this material suitable in a wide range of fields. The application of ND in the biomedical field is attractive but requires more in-depth investigation into the safety of ND and its interactions with different cells and systems. The effects of ND on the immune system are not fully understood or investigated and there are several controverting reports regarding …

Structural And Biochemical Studies Of The Dna Replication Initiation Mechanism Of The Second Chromosome Of Vibrio Cholerae, Natalia Orlova

Dissertations, Theses, and Capstone Projects

Transmission of genetic information through DNA replication is one of the key processes for any living organism. Despite the extensive effort put into studies of the mechanism of DNA replication, the understanding of the process on the molecular level is still incomplete. Specifically the molecular details of the very first events of DNA replication initiation are not sufficiently understood.

The majority of bacteria possess a single circular chromosome, and in order to initiate DNA replication these organisms utilize a conserved system, consisting of a specific DNA sequence - replication origin, called oriC, and replication initiator protein DnaA. However, bacteria …

Identification Of Potential Tissue-Specific Cancer Biomarkers And Development Of Cancer Versus Normal Genomic Classifiers, Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent “OMICS” studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier. Given a sample of a specified tissue type, the single-tissue …

Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim

Journal of Bioresource Management

Typhoid is caused by Salmonella enterica serovar Typhi that is usually diagnosed by using serologic and immuno-chromatographic techniques in developing counties including Pakistan, which is thought to be an unreliable diagnostic method. For accurate diagnosis we used molecular techniques to amplify 204 bp StyR-36 and 498 bp flagellin gene for the identification of Salmonella enterica serovar Typhi. This study was done on 58 individuals diagnosed positive of typhoid via serologic tests and 50 healthy individuals as a control group. Success rate of amplification for flagellin gene was 77.58% while that for StyR-36 gene was 68.97% showing that flagellin gene primer …

Silver Oxide Coatings With High Silver-Ion Elution Rates And Characterization Of Bactericidal Activity., Sarah S Goderecci, Eric Kaiser, Michael Yanakas, Zachary Norris, Jeffrey Scaturro, Robert Oszust, Clarence D Medina, Fallon Waechter, Min Heon, Robert R Krchnavek, Lei Yu, Samuel E Lofland, Renee M Demarest, Gregory A Caputo, Jeffrey D Hettinger

College of Science & Mathematics Departmental Research

This paper reports the synthesis and characterization of silver oxide films for use as bactericidal coatings. Synthesis parameters, dissolution/elution rate, and bactericidal efficacy are reported. Synthesis conditions were developed to create AgO, Ag₂O, or mixtures of AgO and Ag₂O on surfaces by reactive magnetron sputtering. The coatings demonstrate strong adhesion to many substrate materials and impede the growth of all bacterial strains tested. The coatings are effective in killing Escherichia coli and Staphylococcus aureus, demonstrating a clear zone-of-inhibition against bacteria growing on solid media and the ability to rapidly inhibit bacterial growth in planktonic culture. Additionally, the coatings exhibit very …

Homologous Recombination In Protozoan Parasites And Recombinase Inhibitors, Andrew A. Kelso, Sarah M. Waldvogel, Adam J. Luthman, Michael G. Sehorn

Publications

Homologous recombination (HR) is a DNA double-strand break (DSB) repair pathway that utilizes a homologous template to fully repair the damaged DNA. HR is critical to maintain genome stability and to ensure genetic diversity during meiosis. A specialized class of enzymes known as recombinases facilitate the exchange of genetic information between sister chromatids or homologous chromosomes with the help of numerous protein accessory factors. The majority of the HR machinery is highly conserved among eukaryotes. In many protozoan parasites, HR is an essential DSB repair pathway that allows these organisms to adapt to environmental conditions and evade host immune systems …

Evaluation Of The Effect Of Serum Antibody Abundance Against Bovine Coronavirus On Bovine Coronavirus Shedding And Risk Of Respiratory Tract Disease In Beef Calves From Birth Through The First Five Weeks In A Feedlot, Aspen M. Workman, Larry A. Kuehn, Tara G. Mcdaneld, Michael L. Clawson, Carol G. Chitko-Mckown, John Dustin Loy

School of Veterinary and Biomedical Sciences: Faculty Publications

Objective: To evaluate the effect of serum antibody abundance against bovine coronavirus (BCV) on BCV shedding and risk of bovine respiratory disease (BRD) in beef calves from birth through the first 5 weeks in a feedlot.

Animals: 890 natural-service crossbred beef calves from 4 research herds.

Procedures: Serial blood samples for measurement of serum anti-BCV antibody abundance by an ELISA and nasal swab specimens for detection of BCV and other viral and bacterial BRD pathogens by real-time PCR methods were collected from all calves or subsets of calves at predetermined times from birth through the first 5 weeks after feedlot …

Engineered Aptamers To Probe Molecular Interactions On The Cell Surface, Sana Batool, Sanam Bhandari, Shanell George, Precious Okeoma, Nabeela Van, Hazan E. Zümrüt, Prabodhika Mallikaratchy

Publications and Research

Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in …

Crispr/Cas9 In Leishmania Genome Editing : Towards A Proof Of Concept, Zein Kasbo

Theses, Dissertations and Culminating Projects

Leishmaniasis is a parasitic Neglected Tropical Disease (NTD) that affects mostly poor countries of the third word due to their limited access to clean water and health care. The disease is transmitted through the bite of a sand fly of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Historically, NTDs have not been given adequate attention or research funding and finding curative treatments has been slow. However, the fact that the insect vector and the parasite can live and thrive in any ecological system in the world, and under the current circumstances …

Peptide Inhibitors Targeting The Neisseria Gonorrhoeae Pivotal Anaerobic Respiration Factor Ania, Aleksandra E. Sikora, Robert H. Mills, Jacob V. Weber, Adel Hamza, Bryan W. Passow, Andrew Romaine, Zachary A. Williamson, Robert W. Reed, Ryszard A. Zielke, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures …

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to …

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine …

Discovering Antibacterial And Anti-Resistance Agents Targeting Multi-Drug Resistant Eskape Pathogens, Renee Fleeman

USF Tampa Graduate Theses and Dissertations

Antibiotic resistance has been a developing problem for mankind in recent decades and multi-drug resistant bacteria are now encountered that are resistant to all treatment options available. In 2014, the World Health Organization announced that this problem is driving us towards a “post-antibiotic era” that will change the face of modern medicine as we know it. If lack of novel antibiotic development and FDA approval continues, by the year 2050, 10 million people will die each year to an antimicrobial resistant bacterial infection. With lack of pharmaceutical industry involvement in developing novel antibiotics, the responsibility now lies within the academic …