Current Search:  infectious disease (x)

View All Items

  • CSV Spreadsheet
(1 - 8 of 8)
Allelic characterization and novel functions of the outer membrane porin U in Vibrio cholerae
Title
Allelic characterization and novel functions of the outer membrane porin U in Vibrio cholerae.
Creator
Sakib, Sk Nazmus, Almagro-Moreno, Salvador, Moore, Sean, Roy, Herve, University of Central Florida
Abstract / Description
Vibrio cholerae is the etiological agent of the severe diarrheal disease cholera. The bacterium is a natural inhabitant of brackish and estuarine waters . To date, only a subset of V. cholerae strains, those belonging to the pandemic group (PG), can cause cholera in humans while the rest (environmental group, EG) cannot cause the disease. Recently, we discovered that V. cholerae PG contains allelic variations in core genes that confer preadaptation to virulence, which we termed Virulence...
Show moreVibrio cholerae is the etiological agent of the severe diarrheal disease cholera. The bacterium is a natural inhabitant of brackish and estuarine waters . To date, only a subset of V. cholerae strains, those belonging to the pandemic group (PG), can cause cholera in humans while the rest (environmental group, EG) cannot cause the disease. Recently, we discovered that V. cholerae PG contains allelic variations in core genes that confer preadaptation to virulence, which we termed Virulence Adaptive Polymorphisms (VAPs). We identified nine core genes that encode potential VAPs, one of which encodes the outer membrane porin U (OmpU). OmpU provides tolerance to bile and acidic pH, resistance to antimicrobials and facilitates biofilm formation. In this study, several alleles of ompU were analyzed to determine whether these VAPs encode different functional properties. We performed multiple phenotypic assays and observed increased survival for strains encoding the PG-like alleles in the presence of bile, organic acid, anionic detergents and the antimicrobial peptide P2. On the other hand, EG-like alleles only showed increased biofilm formation. Interestingly, tests for motility and tolerance of inorganic acid, polymyxin B and protamine sulphate showed no differences in survival for strains encoding either alleles indicating that some of the properties conferred by OmpU are allelic independent. We have also discovered that V. cholerae OmpU shows resistance against Rifamycin, EDTA and Trifluoperazine and interestingly, Rifamycin has been found to be PG-allele dependent. Our findings provide further evidence that genetic variations in core genes lead to the emergence of virulence adaptive traits in pathogenic V. cholerae and can be extrapolated to other bacterial pathogens.
Show less
Date Issued
2019
Identifier
CFE0007720, ucf:52420
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007720
Mathematical Modeling of Infectious Diseases with Latency: Homogeneous Mixing and Contact Network
Title
Mathematical Modeling of Infectious Diseases with Latency: Homogeneous Mixing and Contact Network.
Creator
Carlson, Keith, Shuai, Zhisheng, Mohapatra, Ram, Guha, Ratan, University of Central Florida
Abstract / Description
In mathematical epidemiology, the standard compartmental models assume homogeneous mixingin the host population, in contrast to the disease spread process over a real host contact network. One approach to incorporating heterogeneous mixing is to consider the population to be a networkof individuals whose contacts follow a given probability distribution. In this thesis we investigate in analogy both homogeneous mixing and contact network models for infectious diseases that admit latency...
Show moreIn mathematical epidemiology, the standard compartmental models assume homogeneous mixingin the host population, in contrast to the disease spread process over a real host contact network. One approach to incorporating heterogeneous mixing is to consider the population to be a networkof individuals whose contacts follow a given probability distribution. In this thesis we investigate in analogy both homogeneous mixing and contact network models for infectious diseases that admit latency periods, such as dengue fever, Ebola, and HIV. We consider the mathematics of thecompartmental model as well as the network model, including the dynamics of their equations from the beginning of disease outbreak until the disease dies out. After considering the mathematical models we perform software simulations of the disease models. We consider epidemic simulationsof the network model for three different values of R0 and compare the peak infection numbers and times as well as disease outbreak sizes and durations. We examine averages of these numbers for one thousand simulation runs for three values of R0. Finally we summarize results and consider avenues for further investigation.
Show less
Date Issued
2016
Identifier
CFE0006276, ucf:51054
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0006276
Modeling Disease Impact of Vibrio-Phage Interactions
Title
Modeling Disease Impact of Vibrio-Phage Interactions.
Creator
Botelho, Christopher, Shuai, Zhisheng, Nevai, A, Zhang, Teng, Teter, Kenneth, University of Central Florida
Abstract / Description
Since the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge(&)nbsp;of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most...
Show moreSince the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge(&)nbsp;of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most commonly affects countries with poor infrastructure and water sanitation. Despite efforts to control cholera in such countries, the disease persists. One such example is Haiti which has been experiencing a cholera outbreak since 2010. While there has been much research in the field of microbiology to understand V. cholerae, there has been comparably less research in the field of mathematical biology to understand the dynamics of V. cholerae in the environment. A mathematical model of V. cholerae incorporating a phage population is coupled with a SIRS disease model to examine the impact of vibrio and phage interaction. It is shown that there might exist two endemic equilibria, besides the disease free equilibrium: one in which phage persist in the environment and one in which the phage fail to persist. Existence and stability of these equilibria are established. Disease control strategies based on vibrio and phage interactions are discussed.
Show less
Date Issued
2019
Identifier
CFE0007604, ucf:52544
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007604
Evolutionary Relationships Among Staphylococci and the Prevention of Staphylococcus aureus Nasal Colonization
Title
Evolutionary Relationships Among Staphylococci and the Prevention of Staphylococcus aureus Nasal Colonization.
Creator
Lamers, Ryan, Cole, Alexander, Parkinson, Christopher, Chai, Xinqing, Moore, Sean, University of Central Florida
Abstract / Description
Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of...
Show moreStaphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that nasal carriage is a major vector for the transmission of virulent strains throughout the community. This hypothesis, however, has not been assessed in any great detail to identify the genetic relationships between clinical isolates of S. aureus and those strains being carried asymptomatically throughout the community. Also lacking within this field is a unified and robust estimate of phylogeny among species of Staphylococcus.Here, we report on a highly unified species phylogeny for Staphylococcus that has been derived using multilocus nucleotide data under multiple Bayesian and maximum likelihood approaches. Our findings are in general agreement with previous reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships. Regardless of methodology, strong nodal support and high topological agreement was observed with only minor variations in results between methods. Based on our phylogenetic estimates, we propose that Staphylococcus species can be evolutionarily clustered into 15 groups, and six species groups. In addition, our more defined phylogenetic analyses of S. aureus revealed strong genetic associations between both nasal carriage strains and clinical isolates. Genetic analyses of hypervariable regions from virulence genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates, but they also exhibited 100% sequence similarity within these regions. Our findings indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of infection and mortality.Due to nasal carriage of S. aureus being a risk factor for autoinfection, standardized preoperative decolonization has become a major consideration for the prevention of nosocomial infection. Toward this end, we have identified the macrocyclic ?-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibited bactericidal effects against S. aureus in both epithelium-free systems, and ex vivo models containing human airway epithelia. Importantly, RC-101 exhibited potent anti-S. aureus activities against all strains tested, including USA300. Moreover, RC-101 significantly reduced the adherence, survival, and proliferation of S. aureus on human airway epithelia without any noted cellular toxicity or the induction of a proinflammatory response. Collectively, our findings identify RC-101 as a potential preventative of S. aureus nasal colonization.
Show less
Date Issued
2011
Identifier
CFE0004124, ucf:49092
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004124
Host and Bacterial Determinants of Staphylococcus aureus Nasal Colonization in Humans
Title
Host and Bacterial Determinants of Staphylococcus aureus Nasal Colonization in Humans.
Creator
Muthukrishnan, Gowrishankar, Cole, Alexander, Moore, Sean, Self, William, Parkinson, Christopher, University of Central Florida
Abstract / Description
Staphylococcus aureus (SA), an opportunistic pathogen colonizing the anterior nares in approximately 30% of the human population, causes severe hospital-associated and community-acquired infections. SA nasal carriage plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage...
Show moreStaphylococcus aureus (SA), an opportunistic pathogen colonizing the anterior nares in approximately 30% of the human population, causes severe hospital-associated and community-acquired infections. SA nasal carriage plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics among a diverse population and determining factors responsible for SA nasal carriage have become major imperatives.Here, we report on an extensive longitudinal monitoring of SA nasal carriage in 109 healthy individuals over a period of up to three years to assess nasal carriage dynamics. Phylogenetic analyses of SA housekeeping genes and hypervariable virulence genes revealed that not only were SA strains colonizing intermittent and persistent nasal carriers genetically similar, but no preferential colonization of specific SA strains in these carriers was observed over time. These results indicated that other non-SA factors could be involved in determining specific carriage states. Therefore, to elucidate host responses during SA nasal carriage, we performed human SA nasal recolonization in a subset of SA nasal carriers within our cohort. In these studies, SA colonization levels were determined, and nasal secretions were collected and analyzed for host immune factors responsible for SA nasal carriage. Interestingly, we observed that stimulation of host immune responses lead to clearance of SA while sustained SA colonization was observed in hosts that did not mount a response during carriage. Further, analysis of nasal secretions from hosts revealed that proinflammatory cytokines and chemokines were significantly induced during SA nasal clearance suggesting that innate immune effectors influence carriage.SA utilizes a repertoire of surface and secreted proteins to evade host immune response and successfully colonize the nose. Analysis of the most abundant immunoevasive proteins in the exoproteome of SA nasal carrier strains revealed that expression levels of Staphylococcal protein A (SPA) produced by SA nasal carrier strains in vitro corresponded to the level of persistence of SA in the human nose. To determine if SPA is involved in modulating the host's response to SA colonization, a subset of participants in our cohort was nasally recolonized with equal concentrations of both wild-type (WT) and spa-disrupted (?spa) autologous strains of SA. Interestingly, ?spa strains were eliminated from the nares significantly faster than WT when the host mounted an immune response, suggesting that the immunoevasive role of SPA is a determinant of carriage persistence. Collectively, this report augments our understanding of SA nasal carriage dynamics, in addition to identifying important host and microbial determinants that influence SA nasal colonization in humans. Better understanding of this phenomenon can lead to improved preventative strategies to thwart carriage-associated SA infections.
Show less
Date Issued
2014
Identifier
CFE0005673, ucf:50173
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005673
Multi-target high-throughput screening assays for antimicrobial drug discovery
Title
Multi-target high-throughput screening assays for antimicrobial drug discovery.
Creator
Grube, Christopher, Roy, Herve, Chakrabarti, Debopam, Moore, Sean, Koculi, Eda, University of Central Florida
Abstract / Description
The rise of antibiotic resistant microbes (bacteria, fungi, and parasites), combined with the current void of new drugs entering the clinical setting, has created an urgent need for the discovery of new antimicrobials. High-throughput screening (HTS) assays represent a fast and cost-efficient method for identifying new therapeutic compounds and have been the longstanding gold standard for drug discovery. The focus of this dissertation is on the development and implementation of novel...
Show moreThe rise of antibiotic resistant microbes (bacteria, fungi, and parasites), combined with the current void of new drugs entering the clinical setting, has created an urgent need for the discovery of new antimicrobials. High-throughput screening (HTS) assays represent a fast and cost-efficient method for identifying new therapeutic compounds and have been the longstanding gold standard for drug discovery. The focus of this dissertation is on the development and implementation of novel methodologies to increase the throughput of target-based HTS by designing assays that allow multiple drug targets to be probed simultaneously. During my graduate studies, I developed three distinct HTS assays. In each of these assays, drug targets were incorporated into synthetic pathways obeying various reaction topologies (e.g., cyclical, parallel, or linear). Each of these reaction topologies conferred specific advantages and limitations to the individual assays. The first assay reconstitutes the bacterial tRNA-dependent pathway for lipid aminoacylation. This two-step pathway combines a tRNA aminoacylation step catalyzed by an aminoacyl-tRNA synthetase (aaRS), and a transferase step, which transfers the amino acid born by the tRNA onto membrane lipids. aaRSs are essential enzymes in all domains of life and represent longstanding drug targets in pathogenic species. The transferase reaction in the pathway is also an appealing drug target since it impacts the cellular permeability of antibiotics. Inhibitors of this reaction could dramatically increase the efficacy of existing therapeutics. The second assay I developed also targets aaRSs, but utilizes a parallel topology that permits the probing of the synthetic and editing activities of up to four aaRSs simultaneously. The third assay utilizes a linear topology that reconstitutes the entire purine salvage pathway from Plasmodium falciparum. Because parasites are unable to synthesize purines de novo, this pathway represents an appealing target for novel antimalarials. Pilot screens using this assay revealed inhibitors for multiple enzymes in the pathway, validating the design of the system. This body of work aims to shift the current paradigm of single-target systems that have historically dominated the HTS field, toward multi-target designs that can be used to more efficiently screen compound libraries against essential pathways in pathogenic microbes.
Show less
Date Issued
2019
Identifier
CFE0007642, ucf:52469
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007642
Light Scattering Property of Gold Nanoparticles with Applications to Biomolecule Detection and Analysis
Title
Light Scattering Property of Gold Nanoparticles with Applications to Biomolecule Detection and Analysis.
Creator
Zheng, Tianyu, Huo, Qun, Zou, Shengli, Gesquiere, Andre, Kang, Hyeran, Zhai, Lei, University of Central Florida
Abstract / Description
Gold nanoparticles (AuNPs) have unique optical and chemical properties. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement. The combined use of AuNPs and DLS has led to a novel analytical assay technology called D2Dx (from diameter to diagnostics). Herein, my dissertation highlights the extended use of D2Dx for biomolecule detection and analysis. Under this general theme, Chapter 1 provides some background information of AuNPs, DLS, the...
Show moreGold nanoparticles (AuNPs) have unique optical and chemical properties. Dynamic light scattering (DLS) is an analytical tool used routinely for nanoparticle size measurement. The combined use of AuNPs and DLS has led to a novel analytical assay technology called D2Dx (from diameter to diagnostics). Herein, my dissertation highlights the extended use of D2Dx for biomolecule detection and analysis. Under this general theme, Chapter 1 provides some background information of AuNPs, DLS, the principle of D2Dx technique and its potential applications. Chapter 2 summarizes a study on the effect of AuNP concentrations and laser power on the hydrodynamic size measurement of AuNPs by DLS. This study demonstrated the multiple scattering effect on DLS analysis, and how to use the exceptionally high sensitivity of DLS in AuNP aggregate detection for bioassay design and development. Chapter 3 explores a cooperative interaction between AuNP and certain proteins in blood serum that are key to the immune system, leading to a novel diagnostic tool that can conveniently monitor the humoral immunity development from neonates to adults and detect active infections in animals. Chapter 4 reports an application of D2Dx technique for acute viral infection detection based on the active immune responses elicited from mouse models infected with influenza virus. Chapter 5 describes another application of D2Dx for prostate cancer detection. The D2Dx assay identifies prostate cancer patients from non-cancer controls with improved specificity and sensitivity than PSA test. Chapter 6 demonstrates the use of AuNPs and DLS for hydrodynamic size measurement of protein disulfide isomerase with two different conformations. Chapter 7 investigates the concentration-dependent self-assembling behavior of ribostamycin through its interaction with AuNPs in aqueous solution. Overall, this dissertation established several lines of applications of using AuNPs and DLS for biomolecular research and in vitro diagnostics.
Show less
Date Issued
2018
Identifier
CFE0007385, ucf:52056
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007385
Infectious Disease Risks in Developing Countries: A Non-Market Valuation Exercise
Title
Infectious Disease Risks in Developing Countries: A Non-Market Valuation Exercise.
Creator
Samajpati, Shreejata, Gerking, Shelby, Dickie, Mark, Caputo, Michael, Roy, Joyashree, University of Central Florida
Abstract / Description
This dissertation focuses on the non-market valuation of health-risks of malaria, an infectious disease that imposes a substantive public health burden across the globe, hitting particularly hard the tropical developing nations of Africa and Asia. The United Nations Millennium Development Goals include malaria control as a priority and large investments are underway to promote effective prevention and treatment. Despite such concerted supply-side efforts, malaria-related mortality and...
Show moreThis dissertation focuses on the non-market valuation of health-risks of malaria, an infectious disease that imposes a substantive public health burden across the globe, hitting particularly hard the tropical developing nations of Africa and Asia. The United Nations Millennium Development Goals include malaria control as a priority and large investments are underway to promote effective prevention and treatment. Despite such concerted supply-side efforts, malaria-related mortality and morbidity still abound due to a complex interface of factors like climate-change, poverty, inadequate control behavior, infection and prevention externalities, parasite resistance etc. This research project digs into the demand-side of the health problem, considers the "externality" dimension to prevention, and primarily asks the question: how do individuals in developing countries view competing disease-control (prevention) measures, viz. a publicly-administered community-level malaria control measure as against private preventive choices. A theoretical model is developed to help explore the public-private interplay of health risks of malaria. The malaria-endemic regions of Kolkata (India) and its rural fringes comprise the site for an empirical investigation. A field survey (Malaria Risk and Prevention Survey, October-December, 2011) incorporating a mix of stated and revealed preference techniques of health valuation is implemented. Risk-perceptions of respondents are elicited using a measurable visual-aid and individuals' perceived valuations of health-risk reductions, randomly offered with the public and private health treatments, are empirically ascertained. Using a Likelihood Ratio Test on the structural risk parameters, it is seen that individuals' valuations of health risk reductions are the same across the private and public treatments. The comparative valuation exercise, thus, corroborates the externality dimension to malaria control, calling for greater public action to combat malaria. The viability of such a scaled-up public malaria program, in the context of Kolkata, is discussed by comparing the public treatment willingness to pay estimates with the annual estimated costs that the Kolkata Municipal Corporation, the civic body in the city of Kolkata, maintains on account of vector control. Results from the comparative valuation exercises also support the idea that private prevention is generally responsive to prevention costs, indicating the importance of price incentives to induce greater prevention. The issues of health valuation and price sensitivity are further explored across various split-samples differentiated on the basis of socio-economic attributes, disease exposure, actual prevention efforts and perceived malaria risks of survey respondents. Such auxiliary exercises help analyze the valuation question in greater depth, and generate policy insights into the potential factors that shape private prevention behavior.
Show less
Date Issued
2012
Identifier
CFE0004594, ucf:49195
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0004594