Antimicrobial peptides from the microbiome as modulators of bacterial virulence

来自微生物组的抗菌肽作为细菌毒力的调节剂

• 批准号: RGPIN-2017-05322
• 负责人: Duperthuy, Marylise
• 金额: $ 1.89万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=649791
• 关键词: Antimicrobial; peptides; microbiome; modulators; bacterial

The gut microbiome has been intensively studied lately because of its fundamental role in human health. However, the molecular dialogue between the bacteria from the microbiome is still poorly understood. My research focus on understanding this dialogue in a cooperative or a competitive bacterial relationship. ******The bacteria from the microbiome are producing antimicrobial peptides (AMPs), which have an important role in regulating the microbial community. The aim of this proposal is to determine if AMPs produced by the microbiome can modulate the expression and secretion of proteins involved in virulence and resistance in V. cholerae. Therefore, our specific objectives are to: ***i) Identify and select bacteria from the microbiome that produce AMP(s) active against V. cholerae. Two approaches will be considered. A random approach consisting of the screening of a bacterial collection from the microbiome for their anti-Vibrio activity, followed by an identification of the producer and a purification of the AMPs. The second approach consist on the selection of the AMPs produced by bacteria from the microbiome based on the available literature, eventually followed by a cloning and purification.***ii) Determine how the AMPs from the microbiome affect the expression and secretion of proteins from V. cholerae. A global proteomic approach will be performed to identify the protein differentially expressed in presence of AMPs. A construction of the mutants of the genes coding for the identified effectors will follow for the identification of the role of the effector proteins in antimicrobial peptide resistance and in virulence using animal models.***iii) Identify the risk of developing a resistance to the AMPs from the microbiome, by cultivating different intestinal pathogens with low concentration of the AMPs from the microbiome.******This work will greatly improve our knowledge of bacteria-bacteria communication in the gut at the molecular level. The novelty resides in considering AMPs as molecules that can subvert the signalling pathways of the neighbouring bacteria, including pathogens, therefore modulating their ability to adapt to their environment.

由于其在人类健康中的基本作用，最近对肠道微生物组进行了深入研究。但是，微生物组细菌之间的分子对话仍然很少了解。我的研究重点是理解合作社或竞争性细菌关系中的对话。 ******微生物组的细菌正在产生抗菌肽（AMP），在调节微生物群落中具有重要作用。该建议的目的是确定微生物组产生的AMP是否可以调节霍乱弧菌中毒力和抗性涉及的蛋白质的表达和分泌。因此，我们的特定目标是：*** i）从微生物组中识别并选择对V.霍乱的活性AMP的细菌。将考虑两种方法。一种随机方法，包括从微生物组中筛选细菌收集的抗颤动活性，然后鉴定生产者和AMP的纯化。第二种方法是根据可用文献从微生物组中选择的AMP的选择，最终是克隆和纯化的。将执行一种全局蛋白质组学方法，以识别在AMPS存在下差异表达的蛋白质。编码为确定的效应子的基因突变体的构造将遵循鉴定效应蛋白在抗菌肽肽抗性中的作用，并使用动物模型来识别效应蛋白的作用。*** iii）确定通过培养不同浓度的Amps litly Insperion的抗Ambi组对AMPS从微生物组中产生抗性的风险，该疗法的浓度为AMP的低浓度llyshimy insps y micry inthiment inthiralion intimention*iii。细菌 - 细菌在分子水平上的肠道通信。新颖性驻留在将AMP视为可以颠覆相邻细菌（包括病原体）的信号通路的分子中，因此调节它们适应环境的能力。