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 扁虱是专职的食血节肢动物，可将多种病原体传播给人类和 家畜。莱姆病，由鹿传播伯氏疏螺旋体引起 在美国，超过95%的病媒传播疾病病例是由肩部硬蜱引起的。尽管 扁虱作为疾病媒介的重要性，阐明了扁虱与病原体关系的分子基础。 落后的原因是我们对扁虱的天然免疫力了解不够全面。我们最近发现了一种抗菌剂 通过水平基因转移从细菌中增选出来的一种肩周炎中的酶。这是驯化的 酰胺酶效应子(Dae2)基因编码一种活性的、溶菌的细胞壁水解酶，该水解酶在肠道和 扁虱的唾液腺。我们发现Dae2具有以前未知的抗菌活性。 扁虱的先天免疫系统，并建议研究其在塑造扁虱-微生物相互作用和 莱姆病病原伯氏杆菌的媒介能力。这项工作将从根本上推进我们的 了解扁虱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壁虱传播感染循环的途径。

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