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Endosymbiont mediated chitin catabolism in the tsetse fly gut impacts trypanosome transmission

采采蝇肠道内共生介导的几丁质分解代谢影响锥虫传播

基本信息

批准号：
10572879
负责人：
BRIAN L WEISS
金额：
$ 26.37万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-11-07 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10572879
关键词：
African Animals Arthropod Vectors Arthropods Bacteria Biological Models Catabolism Chitin Chitinase Chromosomes Communities Culicidae Data Development Disease Disease Vectors Environment Enzymes Epidemiology Epithelium Exhibits Food Genes Genetic Genome Geography Glucosamine Glycosaminoglycans Goals Human In Vitro Infection Ingestion Interdisciplinary Study Investigation Kenya Knock-out Knowledge Laboratories Learning Lectin Leishmania Mediating Midgut Modeling Movement Musca domestica Outcome Parasites Pathogenicity Periodicity Phlebotominae Physiological Physiology Plasmodium Population Prevalence Process Production Proteins Research Role Salivary Glands Sand Flies Structure Symbiosis Taxonomy Ticks Toxin Trypanocidal Agents Trypanosoma Trypanosoma brucei brucei Tsetse Flies Vertebral column Work density disorder control endosymbiont experimental study extracellular fly inhibitor insight migration mutant novel novel strategies overexpression particle pathogen socioeconomics success transmission process vector vector competence vector-borne

项目摘要

The midgut of most arthropods is lined by a peritrophic matrix (PM) that is composed of a chitin backbone upon which assemble a variety of glycosaminoglycans and proteins. The PM serves a defensive role within arthropods by protecting their midgut epithelia from abrasive food particles, regulating the movement of ingested toxins, and serving as a physical barrier against pathogen infection establishment. Some vector-borne protozoan pathogens, including mosquito-transmitted Plasmodium and sand fly-transmitted Leishmania, secrete chitinases that can degrade PM-associated chitin. However, tsetse fly-transmitted African trypanosomes do not produce chitinase, and the mechanism(s) these parasites use to circumvent tsetse’s PM are poorly understood. In addition to potentially being infected with African trypanosomes, all tsetse flies harbor a taxonomically variable community of endosymbiotic bacteria. The success of trypanosome transmission through the tsetse vector depends in part on physiological interactions between the fly and these bacteria. One of tsetse’s endosymbionts, Sodalis glossinidius, exhibits a homogeneous distribution within all laboratory colonized flies and a heterogeneous distribution within and between wild fly populations. Several independent field and laboratory-based studies have repeatedly demonstrated a positive correlation between the presence and density of Sodalis in tsetse’s midgut and the ability of trypanosomes to successfully establish an infection in the fly. The mechanisms that underlie this correlation have never been determined. In this application our interdisciplinary research team will address the hypothesis that a Sodalis secreted endochitinase degrades the chitinous backbone of tsetse’s PM. We speculate that Sodalis-mediated degradation of PM-associated chitin facilitates trypanosome infection establishment in two ways. First, this process would compromise the structural integrity of the PM, thus making it easier for trypanosomes to cross. Second, chitin catabolism results in the production of N-acetyl-D-glucosamine, which is a potent inhibitor of trypanocidal lectins. We propose to use Sodalis mutants that cannot produce endochitinase to functionally characterize the tripartite relationship between the bacterium, tsetse’s PM, and trypanosome infection establishment in the fly’s midgut. Additionally, we propose to use field captured tsetse flies to determine if their Sodalis produce endochitinase that mediates the structural integrity of their tsetse host’s PM. Completion of the experiments proposed in this application will increase our understanding of the basic physiological mechanisms that mediated trypanosome transmission through the tsetse vector and may have translational implications towards the development of novel disease control strategies. Additionally, knowledge obtained herein will be applicable to other arthropod vector model systems (e.g., mosquitoes, ticks, sandflies) that house midgut-associated bacteria and have a PM that pathogens must cross in order to be transmitted to a new vertebrate host.

大多数节肢动物的中肠由由几丁质骨架组成的营养基质（PM）排列