Interactions between coagulase-negative staphylococci and the host

凝固酶阴性葡萄球菌与宿主之间的相互作用

• 批准号: RGPIN-2022-04699
• 负责人: Heinrichs, David
• 金额: $ 3.5万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761030
• 关键词: Interactions; between; coagulase; negative; staphylococci

Mammals are hosts to myriad number of bacteria called the microbiome. Most of these bacteria live in a commensal relationship with us, providing us health, and resistance to pathogenic, or disease-causing, bacteria that we may encounter. My laboratory's research has focused on a group of bacteria known as the staphylococci, which are a group of bacteria made up of approximately 50 species. Most of these species are commensal and do not cause harm, while a handful do have elevated pathogenic potential. The most notorious among these is Staphylococcus aureus which can cause several types of infection and diseases in humans and animals. Our research is centred around understanding the mechanisms by which members of the staphylococci interact with their host, allowing them to survive and thrive on skin and mucosal surfaces which are normally inhospitable to microbes. We examine how these bacteria sense and adapt to their surroundings. These signals include limiting nutrients, host antimicrobials (e.g. fatty acids and peptides), and competing microorganisms. Bacteria that colonize the skin or mucosal membranes of mammals (the host) must be physiologically equipped to survive this inhospitable environment for extended periods. They must also be resistant or tolerant to the host immune system. One of the species of staphylococci, S. lugdunensis, is a noted commensal bacterium. It lives in the nose and can produce an antibiotic that kills S. aureus. Thus, in some circles, this bacterium has been regarded as a probiotic and its use as such has been interrogated. However, its use as a probiotic is contraindicated because of its virulence potential as it can cause infections and sometimes serious. Our research program seeks to identify defining features in this species that distinguish its pathogenic potential. This research program has three aims: Aim1: Define the molecular mechanisms by which S. lugdunensis survives in blood and in immune cells. Aim2: Define the molecular mechanisms by which S. lugdunensis destroys red blood cells and immune cells. Aim3: Define the molecular mechanisms by which S. lugdunensis sticks to host cells or tissues, and how it releases itself so that it may spread to other areas within the host. This discovery-based research program will address important and unique questions concerning key traits of the commensal, yet opportunistic pathogen, S. lugdunensis. The research will provide meaningful and impactful contributions to our understanding of this much understudied bacterium. Along the way, the research program will train many next-generation HQP to become independent thinkers, learners and future leaders. The research, and the HQP thus trained, will have wide-ranging benefits to Canadians. The research is positioned to design and develop better strategies to thwart the spread of antibiotic-resistant bacteria.

哺乳动物是无数细菌的宿主，这些细菌被称为微生物组。这些细菌中的大多数与我们生活在一种共生关系中，为我们提供健康，并抵抗我们可能遇到的致病或致病细菌。我的实验室的研究集中在一组被称为葡萄球菌的细菌上，这是一组由大约50个物种组成的细菌。这些物种中的大多数是寄生虫，不会造成伤害，而少数确实具有较高的致病潜力。其中最臭名昭著的是金黄色葡萄球菌，它可以在人类和动物中引起几种类型的感染和疾病。我们的研究集中在了解葡萄球菌成员与宿主相互作用的机制，使它们能够在通常不适合微生物的皮肤和粘膜表面上生存和生长。我们研究这些细菌如何感知和适应周围环境。这些信号包括限制营养素、宿主抗菌剂（例如脂肪酸和肽）和竞争微生物。在哺乳动物（宿主）的皮肤或粘膜上定居的细菌必须在生理上具备在这种不适宜生存的环境中长时间生存的能力。它们还必须对宿主免疫系统具有抵抗力或耐受性。葡萄球菌属（Staphylococcus）的一个种S. lugdunensis是一种著名的细菌。它生活在鼻子里，可以产生一种抗生素，杀死S。金黄色。因此，在某些圈子里，这种细菌被认为是益生菌，其用途也受到质疑。然而，它作为益生菌的使用是禁忌的，因为它的毒力潜力，因为它可以引起感染，有时严重。我们的研究计划旨在确定该物种的定义特征，以区分其致病潜力。本研究计划有三个目标：目标1：明确S。lugdunensis在血液和免疫细胞中存活。 目的2：明确S. lugdunensis破坏红细胞和免疫细胞。目的3：明确S. lugdunensis粘在宿主细胞或组织上，以及它如何释放自己，以便它可以扩散到宿主内的其他区域。这个发现为基础的研究计划将解决重要和独特的问题，有关的关键性状的寄生虫，但机会致病菌，S。lugdunensis。这项研究将为我们了解这种研究不足的细菌提供有意义和有影响力的贡献。沿着，研究计划将培养许多下一代HQP成为独立的思想家，学习者和未来的领导者。这项研究以及由此培训的HQP将为加拿大人带来广泛的利益。该研究旨在设计和开发更好的策略，以阻止耐药性细菌的传播。