Control of bacterial infections by a horizontally acquired host peptidoglycan amidase

通过水平获得的宿主肽聚糖酰胺酶控制细菌感染

• 批准号: 10306384
• 负责人: BARBARA PANNING
• 金额: $ 39.78万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-14 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10306384
• 关键词: 3-Dimensional; Affect; Amblyomma; Anti-Bacterial Agents; Arthropods; Bacteria; Bacterial Infections; Bite; Black-legged Tick; Blood; Borrelia burgdorferi; Cell Wall; Cells; Controlled Study; Disease; Disease Vectors; Distant; Enzymes; Exclusion; Exhibits; Genes; Genome; Goals; Horizontal Gene Transfer; Human; Hydrolase; Immune; Immunity; In Vitro; Infection; Innate Immune System; Insecta; Integration Host Factors; Livestock; Lyme Disease; Measures; Microbe; Modeling; Molecular; Muramidase; Natural Immunity; North America; Order Spirochaetales; Pathway interactions; Peptidoglycan; Property; RNA Interference; Regulation; Reporting; Research; Role; Salivary Glands; Shapes; Specificity; Structure; Suggestion; Testing; Ticks; Toxic effect; United States; Vector-transmitted infectious disease; Work; Zoonoses; amidase; antimicrobial; arthropod-borne; bactericide; comparative; falls; feeding; human pathogen; immune function; in vivo; insight; knock-down; novel; pathogen; pathogenic bacteria; tick feeding; tick-borne; transmission process; vector; vector competence; vector tick; vector transmission

ABSTRACT Ticks are obligate blood-feeding arthropods that transmit numerous pathogens to both humans and livestock. Lyme disease, which is caused by transmission of the spirochete Borrelia burgdorferi by the deer tick Ixodes scapularis, is responsible for over 95% of vector-borne disease cases in the United States. Despite the importance of ticks as disease vectors, elucidating the molecular basis for tick–pathogen relationships has lagged due to our incomplete understanding of tick innate immunity. We recently identified an antibacterial enzyme in I. scapularis that was co-opted from bacteria through horizontal gene transfer. This domesticated amidase effector (dae2) gene encodes an active, bacteriolytic cell wall hydrolase that is enriched in the gut and salivary glands of ticks. We found that Dae2 affords previously uncharacterized antibacterial activity to the innate immune system of ticks and propose to investigate its role in shaping tick–microbe interactions and vector competence for the Lyme disease pathogen B. burgdorferi. This work will advance our fundamental understanding of how ticks have evolved to selectively control bacteria they transmit and potentially offer new avenues for blocking the tick-borne cycle of infection for an important human pathogen.

摘要 蜱是专性吸血节肢动物，将许多病原体传播给人类和哺乳动物。 牲畜莱姆病，这是由传播螺旋体伯氏疏螺旋体的鹿 在美国，肩突硬蜱是超过95%的病媒传播疾病病例的罪魁祸首。尽管 蜱作为疾病媒介的重要性，阐明了蜱-病原体关系的分子基础， 由于我们对蜱虫先天免疫的不完全理解而落后。我们最近发现了一种抗菌剂 酶在I.肩胛肌是通过水平基因转移从细菌中获得的。这驯化 酰胺酶效应子（DAE 2）基因编码一种活性的溶菌细胞壁水解酶， 蜱的唾液腺我们发现，Dae 2提供了以前未表征的抗菌活性， 蜱的先天免疫系统，并建议研究其在塑造蜱-微生物相互作用中的作用， 莱姆病病原体B的载体能力。burgdorferi。这项工作将促进我们的基本 了解蜱虫如何进化以选择性地控制它们传播的细菌，并可能提供新的 阻断一种重要的人类病原体的蜱传感染循环的途径。

项目成果

Antibacterial potency of type VI amidase effector toxins is dependent on substrate topology and cellular context.

• DOI: 10.7554/elife.79796
• 发表时间: 2022-06-28
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Radkov, Atanas;Sapiro, Anne L.;Flores, Sebastian;Henderson, Corey;Saunders, Hayden;Kim, Rachel;Massa, Steven;Thompson, Samuel;Mateusiak, Chase;Biboy, Jacob;Zhao, Ziyi;Starita, Lea M.;Hatleberg, William L.;Vollmer, Waldemar;Russell, Alistair B.;Simorre, Jean-Pierre;Anthony-Cahill, Spencer;Brzovic, Peter;Hayes, Beth;Chou, Seemay
• 通讯作者: Chou, Seemay