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Full-Text Articles in Medicine and Health Sciences
The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese
The Mechanism Of Human Papillomavirus E7 Protein Mediated S-Phase Reentry In The Squamous Epithelium, Nicholas John Genovese
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Though human papillomavirus infection of the human epidermis is epidemiologically widespread and typically benign, manipulation of the cell cycle within host tissues during infections can predispose the host to malignant neoplastic disease. The frequency of neoplastic progression associated with infection by a particular HPV type is directly related to its risk class; certain virus types are highly prevalent in neoplasia of HPV etiology, whereas other virus types are rarely associated with neoplastic malignancies. Regardless, the gene expression programs of both high-risk and low-risk HPV are sufficient for the production and transmission of viral progeny. In this thesis work we examine …
Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka
Investigation Of Residues Of The Vesicular Stomatitis Virus Nucleocapsid Protein That Affect Transcription And Rna Replication, Djamila Harouaka
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The template for transcription and RNA replication for vesicular stomatitis virus (VSV) and other negative-strand RNA viruses is a ribonucleoprotein (RNP) complex consisting of the viral RNA genome and associated nucleocapsid (N) protein. The structure of the RNP-like complex of VSV showed that the RNA is sequestered between two lobes of the N protein, and adjacent N monomers are linked by an extensive network of interactions. Long-range interactions mediated by the N-terminal arm and C-terminal loop of the N protein stabilize the side-to-side contacts between adjacent N monomers, and are required for RNA encapsidation. It is unclear how the polymerase …
A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang
A Timp2-Armed Conditionally-Replicating Adenovirus For The Treatment Of Ovarian Cancer, Sherry Wei Yang
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Ovarian cancer remains the most lethal gynecological malignancy in the U.S. Conventional therapies have limited therapeutic value due to advanced stage of the disease at diagnosis. Conditionally-replicating adenoviruses (CRAds) are promising, novel anti-cancer agents that are designed to selectively replicate in and lyse tumor cells. In clinical trials, CRAds exhibited limited efficacy thus far. Second generation CRAds are being developed to express a therapeutic protein to further enhance antitumor efficacy. One attractive target in ovarian tumor microenvironment is the matrix metalloproteinases (MMPs) that degrade the extracellular matrix. Thus, tissue inhibitor of metalloproteinase 2 (TIMP2), an endogenous inhibitor of MMPs, is …
Il-21 Dictates The Quality Of The Cd8 T Cell Response During Acute And Chronic Infections, John Seung-Hoon Yi
Il-21 Dictates The Quality Of The Cd8 T Cell Response During Acute And Chronic Infections, John Seung-Hoon Yi
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CD8 T cells contribute to the control of intracellular pathogens including viruses and certain bacteria. Recognition of foreign antigens by antigen-specific CD8 T cells initiates a differentiation process by which CD8 T cells gain effector functions including the ability to rapidly produce cytokines and kill infected cells. Currently, it is not well understood what signals dictate the generation of robust CD8 T cell responses, however it has been demonstrated that without CD4 T cell help CD8 T cell responses are compromised. CD4 T cells are the primary producers of interleukin-21 (IL-21), which has broad immunological actions. Thus for this dissertation, …
The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson
The Role Of Fc Receptor-Like 2 In B Cell Signaling, Tanisha Anne Jackson
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Fc receptor-like 2 (FCRL2) is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus immunoreceptor tyrosine-based inhibitory motifs (ITIM) in addition to a putative immunoreceptor tyrosine-based activation motif (ITAM) sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and ana-lyzed its functional potential to show that coligation with the B cell receptor (BCR) leads to tyrosine phosphorylation of its ITIM motifs and subsequent SHP-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are …
Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis
Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis
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Porphyromonas gingivalis is a main causative agent for adult chronic periodontitis and immunization with its virulence factor Hemagglutinin B (HagB) provides protection against infection. Toll-like receptors (TLRs) recognize various microbial products and are crucial in eliciting and regulating the innate and adaptive immune responses to infections. The objective of this dissertation was to investigate the cellular mechanisms that influence the innate and adaptive immune response to HagB and P. gingivalis, focusing on the role of TLR signaling in the response. We started with investigating the ability of HagB to activate dendritic cells (DC), the most efficient antigen-presenting cell in priming …
Translocation And Function Of Akt In The Mitochondria, Keri A. Mans
Translocation And Function Of Akt In The Mitochondria, Keri A. Mans
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The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …
O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho
O-Glcnac Transferase Modulates Jnk1 And Foxo4 Transcription Factor To Resist Acute Oxidative Stress, Shiuh-Rong Ho
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O-GlcNAcylation is an abundant and dynamic post-translational modification on serine and threonine residues of nuclear and cytoplasmic proteins. O-GlcNAc Transferase (OGT) and Nuclear Cytoplasmic O-GlcNAcase and Acetyltransferase (NCOAT) are the only two enzymes and major regulators in this process. In the past two decades, many studies have demonstrated its important modulation roles in nutrient sensing, protein turnover, cell cycle progression, transcription, translation as well as stress resistance. Among these biological functions, the understanding of O-GlcNAcylation dependent oxidative stress is relatively unknown. This study aims to examine the effects of O-GlcNAcylation on JNK1 and FOXO4 transcription factors under acute oxidative stress …
The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett
The Contribution Of Different Mechanisms Of Viral Sequence Variation To The Evolution Of Positive-Sense Single-Stranded Rna Viruses, Brett Earl Pickett
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The Flaviviridae family of positive-sense single-stranded RNA (+ssRNA) viruses includes viral taxa which greatly impact public health worldwide. To explore how the viruses within the Flaviviridae family evolve, we examined the extent to which these viral taxa use nucleotide covariance, spontaneous mutation, and/or homologous recombination to vary their genotype as well as the resulting phenotype. We developed and used CovarView to assist us in simultaneously viewing and inspecting the results from whole genome covariance analyses. This resulted in the identification of previously-characterized RNA functional structures in the genomes of hepatitis C virus (HCV), as well as a new RNA functional …
Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher
Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher
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Serogroup 6 of Streptococcus pneumoniae has been known to contain three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase (wciNα), which has been replaced with a glucosyltransferase (wciNß) in the 6C capsule gene locus. We considered that a new serotype, 6D, would be possible if the glucosyltransferase found in 6C strains was combined with the wciP gene from a 6B strain. We demonstrate that this gene combination yields …
The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar
The Role Of Socs Proteins In Hiv Immune Evasion, Lisa Nowoslawski Akhtar
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Upon human immunodeficiency virus (HIV) infection the host mounts a robust and multifaceted immune response. To achieve successful replication, HIV must possess a powerful arsenal of immune evasion weapons. While a complex strategy for HIV immune evasion has been described in the periphery, little is known about the mechanism allowing HIV to overcome the simple interferon (IFN)-ß-mediated innate immune defenses of the central nervous system (CNS). In light of the devastating cognitive dysfunction that is caused by HIV replication within the CNS, a better understanding of this mechanism is critical. Recent studies have shown that viral pathogens can induce the …
Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng
Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng
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Host immune responses to the commensal microbiota are tightly controlled. Multiple levels of regulation reinforce intestinal homeostasis, including regulation by mucosal dendritic cells (DCs), regulatory T (Treg) cells, and the microbiota itself. However, the mechanisms involved are still largely unknown. Our current studies indicate that mucosal DCs originate and develop in the bone marrow, the latter of which is driven by retinoic acid (RA). Bone marrow cells express the RA-synthesizing enzyme ALDH, and provide RA to DC precursors in the bone marrow niche. RA induces DCs to express gut-homing CCR9 and ALDH1a2, and endows them with the ability to promote …
The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley
The Role Of Wnt5a In Mammary Gland Development, Sarah Baxley
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Transforming growth factor-beta (TGF-beta) negatively regulates mammary gland development and requires Wnt5a to exert some of these effects on mammary gland development. Wnt5a is a non-canonical signaling Wnt that is expressed in all stages of mammary gland development except lactation. Using slow release pellets containing Wnt5a, as well as Wnt5a null tissue, we previously showed that Wnt5a also acts to limit mammary development. Initial studies revealed a potential role for TGF-beta and Wnt5a in regulating mammary gland progenitor cells, indicating they may act to regulate the stem and progenitor cell population. In order to study the role of Wnt5a on …
Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy
Visualizing The Productive Program Of Hpv In Differentiating Squamous Epithelial Tissue, Aaron A. Duffy
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The human papillomavirus (HPV) establishes persistent infections in the basal stratum of squamous epithelia, while productive amplification of viral DNA occurs in differentiated keratinocytes prior to virion assembly in the superficial strata. Until recently, only in situ hybridization (ISH) of low-grade HPV lesions could be used to reveal a snap shot of the viral life cycle. There has been a critical need to reproducibly propagate HPV infections in culture for consistent genetic analyses. Organotypic raft cultures recapitulate a differentiated squamous epithelium. Our lab utilized in vivo Cre-mediated recombination to reconstitute the entire HPV-18 genome in primary human keratinocytes (PHKs). My …
Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar
Development Of A Mucosal Vaccine Protective Against Francisella Tularensis Infection, Amit R. Ashtekar
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Francisella tularensis, a facultative intracellular, gram-negative coccobacillus, is the causative agent of tularemia and has been classified as a category A biological agent. Since there currently is no licensed vaccine available, in this study, we assessed the potential of a bivalent subunit vaccine comprising of DnaK and Tul4 to protect against respiratory tularemia. Intranasal immunization of C57BL/6 mice with DnaK, Tul4, and the adjuvant GPI-0100 resulted in mucosal and systemic antibody responses to DnaK and Tul4. In addition to antibody responses, this immunization regimen also induced both Th1 and Th2 cell-mediated immune responses specific for DnaK and Tul4. Finally, more …
Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani
Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani
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The ability to differentially manipulate available genetic information in order to generate diverse cellular identities represents an innovation of complex multicellular eukaryotic organisms. Cis-acting modules that regulate transcription play extremely important roles in ensuring lineage-specific expression of genes that define cellular identities. In our studies, using Interferon-gamma (IFN-gamma, a cytokine encoded by the gene Ifng), a cytokine encoded by T, NK and NKT cells as a model, we have identified and characterized the roles of key cis regulatory elements that facilitate T lineage specific induction as well as repression of Ifng transcription. In particular, our studies have highlighted the role …
Regulation Of The Acid-Sensing Ion Channel 1 By Protein Kinase C And Matriptase, Edlira Bashari
Regulation Of The Acid-Sensing Ion Channel 1 By Protein Kinase C And Matriptase, Edlira Bashari
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Acid-sensing ion channel 1 (ASIC1) is a member of the Epithelial Na+ channel/ Degenerin (ENaC/Deg) family of ion channels. Like the other members of this family, it is sensitive to the diuretic amiloride. It was previously shown that both normal astrocytes and glioma cells express ASIC1 and some ENaC subunits. However, only high-grade glioma cells exhibit an inward Na+ current that is sensitive to amiloride and to psalmotoxin 1 (PcTX-1), a specific blocker of ASIC1. Amiloride, PcTX-1, and the knockdown of ASIC1 reduce glioma cell migration. The exact composition of the amiloride-sensitive channel and the molecular mechanisms that regulate its …
Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle
Canonical Wnt Signaling By The Proteolytic Processing Of Lrp6, Brandon Richard Beagle
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Low density Lipoprotein receptor Related 6 (LRP6) functions as an essential co-receptor for Wnt/Beat;-catenin signaling as pathway activation, reflected by cytosolic Beta-catenin stabilization and TCF/LEF-1 transactivation, requires Glycogen Synthase Kinase 3Beta(GSK3Beta)-mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane anchored LRP6 intracellular domain. Additionally, LRP6 undergoes a proteolytic cleavage event resulting in the formation of a soluble LRP6 intracellular domain (LRP6-ICD). LRP6-ICD can function within the Wnt/Beta-catenin pathway by interacting with GSK3Beta and attenuating the phosphorylation of GSK3Beta substrates such as cytosolic Beta-catenin as well as stimulate TCF/LEF-1 activity. However, LRP6-ICD's role(s) within the Wnt/Beta-catenin pathway and the mechanism(s) that …
Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine
Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine
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Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …
Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben
Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben
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ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL CHANNELS IN GLIOMA CELL BIOLOGY VALERIE C. BOMBEN DEPARTMENT OF NEUROBIOLOGY ABSTRACT Gliomas, primary brain tumors derived from glial cells, constitute the majority of malignant tumors within the central nervous system. The most malignant of these tumors, grade IV Glioblastoma multiforme, are characterized by extensive proliferation, cellular and nuclear atypia, angiogenesis, areas of necrosis, and widespread invasion into the brain parenchyma. Data from our lab and others have implicated ion channels in the invasion and proliferation of glioma cells. Moreover, calcium signaling in gliomas and other cells has been implicated in both migration and …
Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty
Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty
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Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …
Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker
Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker
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The bacterial chromosome is dynamic. The principle goal of my research is to understand how DNA topology is altered by transcription in Salmonella enterica serovar Typhimurium LT2. Gamma delta-resolution requires two direct repeat Res sites to pair a plectonemic synapse. Previous work from our lab showed that the zones of high transcription inhibited gamma delta-resolution. Using phage λ recombineering methods, we have developed Salmonella strains to study ribosomal RNA operons, which are the most highly transcribed genes in bacteria. We propose a molecular model for how supercoiling generated by high levels of transcription modifies chromosome structure.
Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke
Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke
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Apoptosis, or programmed cell death, is essential for the development and maintenance of mammalian tissues. Activation of cysteinyl aspartate specific proteases, called caspases, is crucial to the implementation apoptosis. During apoptosis, the second mito-chondrial derived activator of caspase (Smac), augments caspase activity by antagonizing the inhibitor of apoptosis proteins (IAPs) down-regulation of caspase function. Smac protein synthesis occurs in the cytosol from a nuclear gene. Mitochondrial import of Smac leads to proteolytic removal of the first 55 amino acids, exposing a novel amino-terminus composed Ala56-Val-Pro-Ile59, which is an inhibitor of apoptosis binding motif (IBM). The IBM facilitates the interactions with …
The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen
The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen
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The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …
Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen
Cathelin-Related Antimicrobial Peptide (Cramp) Regulates B Cell Igg1 Production, Yao Chen
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Mammalian antimicrobial peptides, including cathelicidins and defensins, play an important role in host defense via direct antimicrobial activity as well as immune regula-tion. The cathelin-related antimicrobial peptide (mCRAMP) is the only identified mouse cathelicidin and the orthologue of human LL-37. We show that all mouse B cell subsets, including follicular, marginal zone, B1a, and B1b cells, as well as CD4+ and CD8+ T cells produce mCRAMP directly ex vivo. In addition, mCRAMP-deficient B cells produced less IgG1 antibody in vitro in response to CD40L or LPS plus IL-4 when compared to WT B cells. The addition of recombinant mCRAMP at …
The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang
The Effects Of Environmental Ozone Exposure On Vascular Function, Oxidative Stress, And Atherosclerosis, Gin Chuang
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Exposure to air pollutants are known to induce airway inflammation, decrease lung function, and worsen existing pulmonary conditions such as asthma. Additionally, air pollutant exposure has also been shown to impact cardiovascular health. Although these pollutant-induced cardiovascular effects were considered to be mediated by the direct action of pollutants upon the cardiovascular tissue and/or the indirect release of pro-inflammatory factors into the circulation, the relative contribution of the two pathways remained equivocal. Recently, several epidemiology studies associated ozone exposure with cardiovascular mortalities. However, relatively few studies to date have examined ozone in this context. In order to address our hypothesis …
The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark
The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark
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Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …
Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels
Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels
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Current pneumococcal vaccines containing pneumococcal capsular polysaccharide antigens protect against infection by pneumococci. However, this protection is limited to strains expressing the capsule types included in the vaccine. Since the introduction of these vaccines, the increase in incidence of infection by serotypes not targeted by the vaccine, a process called "serotype replacement," and the growing antibiotic resistance of replacement strains both stress the need for vaccines with broader protection. The alpha-helical region of a protein present on all clinical isolates of pneumococci, Pneumococcal Surface Protein A (PspA), elicits protective immunity. Downstream of the alpha-helical region is a highly conserved region …
The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan
The Role Of Post-Translational Modifications And Valosin-Containing Protein In The Turnover And Stability Of The Microtubule-Associated Protein Tau, Philip James Dolan
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Alzheimer Disease (AD) is pathologically characterized by the appearance of senile plaques composed of ß-amyloid and neurofibrillary tangles composed of the microtubule-associated protein tau. During the development of AD pathology, tau is hyperphosphorylated and aberrantly cleaved, both of which potentially contribute to its pathogenic and fibrillogenic nature. The accumulative nature of these post-translational products, and their contribution to tau pathology, has led to a great deal of study regarding mechanisms for both the maintenance of tau stability and degradation. The first part of this study reviews the developments regarding the contribution of phosphorylated tau to different physiological and pathological processes. …
Characterization Of The Oligosaccharides Of B. Anthracis Exosporium, Shengli Dong
Characterization Of The Oligosaccharides Of B. Anthracis Exosporium, Shengli Dong
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Fatal systemic anthrax is caused by exposure to spores of Bacillus anthracis. The outermost layer of the B. anthracis spore is called the exosporium. It consists of a paracrystalline basal layer and an external hair-like nap. The filaments of the hair-like nap are primarily composed of the glycoprotein BclA. Our previous studies showed that a 715-Da tetrasaccharide and a 324-Da disaccharide are attached to BclA through GalNAc. We named the novel nonreducing terminal sugar of the 715-Da tetrasaccharide anthrose. We subsequently proposed a plausible anthrose biosynthetic pathway and identified a gene cluster of four continuous genes that appeared to encode …