Investigations of the role of host controlled peptidoglycan recycling in the regulation of the pea aphid-Buchnera symbiosis

宿主控制的肽聚糖回收在豌豆蚜-Buchnera 共生调节中的作用研究

• 批准号: 10228362
• 负责人: Thomas E Smith
• 金额: $ 1.73万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-09 至 2020-12-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228362
• 关键词: Affect; African Trypanosomiasis; Animal Model; Animals; Antibiotics; Aphids; Back; Bacteria; Binding; Biochemical; Biochemical Genetics; Biological Assay; Bordetella pertussis; Buchnera; Buchnera aphidicola; Cardiovascular Diseases; Cell Wall; Cell division; Cells; Chagas Disease; Communication; Development; Disease; Domestic Animals; Engineering; Enzymes; Equilibrium; Eukaryota; Gene Expression; Gene Expression Profile; Genes; Genetic; Genome; Genotype; Goals; Homeostasis; Human; Immunofluorescence Immunologic; In Vitro; Infection; Inflammatory Bowel Diseases; Insecta; Invaded; Investigation; Knowledge; Lead; Light; Link; Membrane; Microbe; Modeling; Neisseria gonorrhoeae; Nutritional; Obesity; Pathogenicity; Pathway interactions; Peptidoglycan; Phenotype; Pisum; Pisum sativum; Play; Population; Population Sizes; Prevention; Process; Prokaryotic Cells; Proteins; Proteomics; Recombinants; Recycling; Regulation; Role; Serratia; Signal Pathway; Small Interfering RNA; Structure; Substrate Specificity; Symbiosis; System; Testing; Variant; Vesicle; Vibrio fischeri; Work; base; body cavity; cell envelope; commensal bacteria; experimental study; fitness; flexibility; gene function; gene product; genetic approach; genome-wide; gut microbiome; human disease; in vivo; insect disease vector; insight; microbial; microorganism interaction; new therapeutic target; novel; novel strategies; novel therapeutics; pathogen; pathogenic bacteria; response; symbiont; tool; transcriptomics

Project Summary Animals live in close association with bacteria, including both beneficial symbionts and harmful pathogens. Understanding the nuances that enable hosts to respond differently to pathogenic versus beneficial interactions could enable therapies that specifically target pathogens. A fundamental interface between bacterial and animal cells is the bacterial cell wall. In particular, cell wall peptidoglycan (PG) is known to be a key molecule in the infection process, both for pathogens such as Bordetella pertussis and Neisseria gonorrhoeae and also for symbionts such as Vibrio fischeri. In the model symbiosis of the pea aphid, Acyrthosiphon pisum, with its bacterial symbiont, Buchnera aphidicola, key enzymes in the pathway for PG recycling are encoded in the host genome and are known to be specifically expressed in the cells that harbor the symbiotic bacteria, and similar observations have been made in other eukaryotic systems. The focus of this proposal is to test the novel hypothesis that host control of PG recycling is a key mechanism for host regulation of symbiont populations. We will test this hypothesis using novel biochemical and genetic approaches within the pea aphid system. Specifically, we hypothesize that variation in Buchnera abundance between aphids can be explained by differences in the level of host-derived PG gene expression, that the host employs proteins that alter the Buchnera cell wall, and that host control over Buchnera PG recycling establishes stability of Buchnera population sizes. Testing this hypothesis will shed light on how animals domesticate pathogenic bacteria and convert them into symbionts, and, more broadly, will expand our fundamental understanding of microbial interactions with animals, including humans. To define the role of PG recycling in the regulation of symbiosis, we will: 1) investigate whether PG- related host genes play a role in determining Buchnera population size, 2) determine how host PG-related genes interact functionally with the Buchnera cell wall, and 3) demonstrate the relationship between host PG genes and Buchnera regulation in vivo. To test this, we will quantify the differences in PG gene expression levels between aphid genotypes with high versus low Buchnera abundance, characterize how host gene products affect Buchnera PG in vitro, and interrogate PG gene functions in vivo, implementing novel genetic tools for the aphid-Buchnera system. We predict that aphids use PG genes to disrupt Buchnera PG recycling and halt cell division, enabling hosts to control symbiont abundance by negative regulation. Our genome-scale approaches will enable discovery of other potential genetic bases of symbiont control. Results of the proposed work will contribute significantly to our understanding of how animals interact with symbiotic bacteria and, more specifically, how hosts regulate symbionts. These findings may lead to novel drugs targeting bacterial symbionts of insect disease vectors, or to the development of antibiotics that do not harm beneficial symbionts.

项目总结

项目成果

Horizontal-Acquisition of a Promiscuous Peptidoglycan-Recycling Enzyme Enables Aphids To Influence Symbiont Cell Wall Metabolism.

• DOI: 10.1128/mbio.02636-21
• 发表时间: 2021-12-21
• 期刊: mBio
• 影响因子: 6.4
• 作者: Smith TE;Lee M;Person MD;Hesek D;Mobashery S;Moran NA
• 通讯作者: Moran NA