A5023018526- Vector-borne infectious diseases
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Vector-Borne Animal Diseases
- Insect symbiosis and bacterial influences
- Oral microbiology and periodontitis research
- Yersinia bacterium, plague, ectoparasites research
- Toxin Mechanisms and Immunotoxins
- Leptospirosis research and findings
- Insect and Pesticide Research
- Immune Response and Inflammation
- Trypanosoma species research and implications
- Antimicrobial Peptides and Activities
- Neuroinflammation and Neurodegeneration Mechanisms
- Bacterial biofilms and quorum sensing
- Bacteriophages and microbial interactions
- Heat shock proteins research
- Epigenetics and DNA Methylation
- HIV/AIDS oral health manifestations
- Bartonella species infections research
- Cerebrospinal fluid and hydrocephalus
- Neurogenesis and neuroplasticity mechanisms
- Polydiacetylene-based materials and applications
- Cancer-related gene regulation
- Parasitic Infections and Diagnostics
University of North Dakota
2015-2024
University of Kentucky
2007-2012
Albert B. Chandler Hospital
2008
University of Washington
2002
University of Vermont
1999
The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway complement-mediated killing, interact with various extracellular matrix (ECM) components. LenA outer surface protein (formerly called LfhA Lsa24) was previously shown bind ECM component laminin complement regulators factor H H-related protein-1. We now...
ABSTRACT Host-derived plasmin plays a critical role in mammalian infection by Borrelia burgdorferi . The Lyme disease spirochete expresses several plasminogen-binding proteins. Bound plasminogen is converted to the serine protease and thereby may facilitate bacterium's dissemination throughout host degrading extracellular matrix. In this work, we demonstrate binding three highly similar borrelial outer surface proteins, ErpP, ErpA, ErpC, all of which are expressed during infection. Extensive...
Borrelia burgdorferi is the causative agent of Lyme disease, most commonly reported arthropod-borne disease in United States. B. a highly invasive bacterium, yet lacks extracellular protease activity. In order to aid its dissemination, binds plasminogen, component hosts' fibrinolytic system. Plasminogen bound surface can then be activated plasmin, facilitating bacterium's penetration endothelial cell layers and degradation matrix components. Enolases are conserved proteins with no sorting...
The Lyme disease spirochete, Borrelia burgdorferi, is largely resistant to being killed by its hosts' alternative complement activation pathway. One possible resistance mechanism of these bacteria coat their surfaces with host regulators, such as factor H. Five different B. burgdorferi outer surface proteins having affinities for H have been identified: regulator-acquiring protein 1 (BbCRASP-1), encoded cspA; BbCRASP-2, cspZ; and three closely related proteins, BbCRASP-3, -4, -5, erpP, erpC,...
ABSTRACT Borrelia burgdorferi , the Lyme disease-causing spirochete, can persistently infect its vertebrate hosts for years. B. is often found associated with host connective tissue, where it interacts components of extracellular matrix, including fibronectin. Some years ago, a borrelial surface protein, named BBK32, was identified as fibronectin-binding protein. However, BBK32 mutants are still able to bind fibronectin, indicating that spirochete possesses additional mechanisms adherence We...
ABSTRACT The spirochete Leptospira interrogans is a highly invasive pathogen of worldwide public health importance. Studies from our laboratories and another have demonstrated that L. can acquire host plasminogen on its surface. Exogenous activators then convert bound into the functionally active protease plasmin. In this study, we extend upon those observations report leptospiral endostatin-like protein A (LenA) binds human in dose-dependent manner. LenA-plasminogen interactions were...
Borrelia burgdorferi, the agent of Lyme disease, differentially expresses numerous genes and proteins as it cycles between mammalian hosts tick vectors. Insights on regulatory mechanisms have been provided by earlier studies that examined B. burgdorferi gene expression patterns during cultivation. However, prior bacteria at only a single time point cultivation, providing snapshot what is likely dynamic transcriptional program driving adaptations to changes culture growth phases. To address...
Lyme disease, which is caused by infection with Borrelia burgdorferi and related species, can lead to inflammatory pathologies affecting the joints, heart, nervous systems including central system (CNS). Inbred laboratory mice have been used define kinetics of B . host immune responses in joints however similar studies are lacking CNS these animals. A tractable animal model for investigating host- interactions key understanding mechanisms pathogenesis. Therefore, we characterized...
The Lyme disease spirochaete, Borrelia burgdorferi, can invade and persistently infect its hosts' connective tissues. We now demonstrate that B. burgdorferi adheres to the extracellular matrix component laminin. surface-exposed outer-membrane protein ErpX was identified as having affinity for laminin, is first laminin-binding be in a spirochaete. adhesive domain of shown contained within small, unstructured hydrophilic segment at protein's centre. sequence distinct from any previously...
The Borrelia burgdorferi BmpA outer surface protein plays a significant role in mammalian infection by the Lyme disease spirochete and is an important antigen for serodiagnosis of human infection. B. adheres to host extracellular matrix components, including laminin. results our studies indicate that its three paralogous proteins, BmpB, BmpC, BmpD, all bind did not type I or IV collagens fibronectin. BmpA-directed antibodies significantly inhibited adherence live laminin-binding domain was...
Prokaryote restriction modification (RM) systems serve to protect bacteria from potentially detrimental foreign DNA. Recent evidence suggests that DNA methylation by the methyltransferase (MTase) components of RM can also have effects on transcriptome profiles. The type strain causative agent Lyme disease, Borrelia burgdorferi B31, possesses two with N6-methyladenosine (m6A) MTase activity, which are encoded bbe02 gene located linear plasmid lp25 and bbq67 lp56. specific recognition and/or...
ABSTRACT Nearly every known species of Eubacteria encodes a homolog the Borrelia burgdorferi EbfC DNA-binding protein. We now demonstrate that fluorescently tagged associates with B. nucleoids in vivo and chromatin immunoprecipitation (ChIP) wild-type showed it to bind sites throughout genome, two hallmarks nucleoid-associated proteins. Comparative RNA sequencing (RNA-Seq) mutant strain overexpresses indicated approximately 4.5% borrelial genes are significantly impacted by EbfC. The ebfC...
Abstract The PilZ domain‐containing protein, PlzA, is the only known cyclic di‐GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in regulation of many borrelial processes, but effector mechanism was not previously known. Here, we report that can bind DNA and RNA nucleic acid requires c‐di‐GMP, with affinity for acids increasing as concentrations c‐di‐GMP were increased. A mutant incapable did to any tested acids. We also determined interacts predominantly...
The Lyme disease spirochete, Borrelia burgdorferi, encodes a novel type of DNA-binding protein named EbfC. Orthologs EbfC are encoded by wide range bacterial species, so characterization the borrelial has implications that span eubacterial kingdom. present work defines DNA sequence required for high-affinity binding to be 4 bp broken palindrome GTnAC, where 'n' can any nucleotide. Two EbfC-binding sites located immediately 5′ B. burgdorferi erp transcriptional promoters, and was found alter...
ABSTRACT Vector-borne pathogens regulate their protein expression profiles, producing factors during host infection that differ from those produced vector colonization. The Lyme disease agent, Borrelia burgdorferi , produces Erp surface proteins throughout mammalian and represses synthesis colonization of ticks. Known functions include binding laminin, plasmin(ogen), regulators complement activation. A DNA region immediately 5′ erp operons, the operator, is required for transcriptional...