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Borrelia gene products critical for natural infection cycle

疏螺旋体基因产物对自然感染周期至关重要

基本信息

批准号：
10659166
负责人：
UTPAL PAL
金额：
$ 48.67万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10659166
关键词：
Amino Acids Anti-Infective Agents Antibiotic Therapy Antigens Arthropod Vectors Bacteria Binding Biological Biological Products Biology Black-legged Tick Borrelia Borrelia burgdorferi Borrelia burgdorferi Group C-terminal Cells Chronic Clinical Complex Crystallization Development Dimensions Early Diagnosis Epitopes Europe Event Genome Goals High temperature of physical object Human Impairment Infection Infection Control Investigation Ixodes Knowledge Length Lyme Disease Mammals Measures Mediating Membrane Membrane Proteins Molecular Chaperones N-terminal Nature Order Spirochaetales Pathogenesis Peptide Hydrolases Peptidoglycan Pharmaceutical Preparations Phase Post Treatment Lyme Disease Syndrome Process Protein Inhibition Proteins Proteolytic Processing Recombinants Relapse Rodent Role Series Spirochaetales Infections Structure Symptoms Therapeutic Tick Infestations Tick-Borne Infections Ticks Translation Process United States Vaccines Virulence antimicrobial combat design enzootic experience extracellular gene conservation gene product insight lyme pathogenesis microbial novel novel therapeutic intervention novel therapeutics novel vaccines pathogen pathogenic bacteria patient subsets polypeptide protein function protein protein interaction small molecule standard care tick transmission tick-borne transmission process vaccine development vector tick

项目摘要

PROJECT SUMMARY/ABSTRACT Lyme borreliosis, also known as Lyme disease, remains a prevalent tick-borne infection in many parts of the world. In the United States alone, there are over 300,000 new cases occurring each year. The infection is caused by Borrelia burgdorferi sensu lato, which is a group of atypical extracellular bacterial pathogens that survive in nature through a complex enzootic infection cycle, involving ticks belonging to the Ixodes scapularis complex and an array of vertebrate hosts, most commonly wild rodents. Despite serious efforts to control the infection over the past several decades, the infection persists, largely due to the absence of effective control measures against tick infestation, lack of human vaccines, difficulties in diagnosis of early infection, and clinical complications associated with treatment using currently-available antimicrobials. Specifically, several months after standard-care antibiotic therapy, a subset of patients can experience a series of persistent or relapsing symptoms, known as chronic Lyme disease or post-treatment Lyme disease syndrome, for which further treatment options remain unavailable. Therefore, the development of vaccines and new drugs is highly warranted to combat Lyme disease. This project pursues a long-term goal to understand the biological significance of a critical set of microbial virulence determinants and gain knowledge necessary for the development of new therapeutic strategies to intervene with Lyme borreliosis. The emphasis is on protein- protein interactions essential for pathogen infection and persistence in the host, and the goal is to provide comprehensive structural and functional information that defines the biological significance of three spirochete proteins annotated as BB0323, BB0238, and BB0104 (BbHtrA), each of which either independently or as a complex are essential for infection. The previous project cycle demonstrated that the targeted deletion or alteration of either protein partners or short binding epitopes impact protein stability and render the pathogen non-infectious in a mammalian host. The overall objective of the current proposal is to further focus on BB0323 and associated proteins in order to: 1) define the specific events of protein maturation, 2) determine protein-protein interactions, and 3) contribute to the determination of their structures to better understand their roles in dictating spirochete infection in mammals and transmission from ticks. These studies will enlighten our fundamental knowledge of the atypical biology of spirochetes and will facilitate the design of non-traditional anti-infective strategies to combat Lyme borreliosis, including the development of vaccines, small molecule drugs, and biologics.

项目总结/文摘

项目成果

期刊论文数量（49）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

BBA52 facilitates Borrelia burgdorferi transmission from feeding ticks to murine hosts.

DOI：
10.1086/651172
发表时间：
2010-04-01
期刊：
The Journal of infectious diseases
影响因子：
0
作者：
Kumar M;Yang X;Coleman AS;Pal U
通讯作者：
Pal U

Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling.

DOI：
10.1128/msystems.00927-23
发表时间：
2023-12-21
期刊：
mSystems
影响因子：
6.4
作者：
通讯作者：

A systemic approach to identify non-abundant immunogenic proteins in Lyme disease pathogens.

DOI：
10.1128/msystems.01087-23
发表时间：
2024-01-23
期刊：
MSYSTEMS
影响因子：
6.4
作者：
Yas, Ozlem Buyuktanir;Coleman, Adam S.;Lipman, Rachel M.;Sharma, Kavita;Raghunandanan, Sajith;Alanazi, Fuad;Rana, Vipin S.;Kitsou, Chrysoula;Yang, Xiuli;Pal, Utpal
通讯作者：
Pal, Utpal

Function and evolution of the aquaporin IsAQP1 in the Lyme disease vector Ixodes scapularis