Defining the role of membrane stability in the ability of Staphylococcus aureus to form part of the human microbiome

背景：人体微生物群系由所有与我们共生的微生物组成，这些微生物存在于我们身体的非无菌部分，包括我们的皮肤、呼吸道、消化道和泌尿生殖系统。这些部位的微生物群的组成对我们的健康至关重要，因此干扰会增加我们对许多炎症性和传染性疾病的易感性。尽管它很重要，但我们对微生物群中的细菌如何在免疫系统的攻击下保持其存在以及面对来自其他微生物的竞争的理解仍不清楚。然而，一个可能是关键的特征是它们快速感知和应对环境变化的能力。作为单细胞生物体，细菌的这种能力完全依赖于它们的膜，特别是这种膜的稳定性，因为它充当了嵌入在那里的所有蛋白质和分子的平台，这些蛋白质和分子使细菌能够感知和反应。模式生物：金黄色葡萄球菌是鼻腔和皮肤微生物群中的一员，约占人类人口的30%。有几个分子已被确定在金黄色葡萄球菌的膜稳定性中起关键作用，包括其特有的金黄色色素葡萄糖素，以及最近发现的一种小蛋白(105个残基)，它是细菌膜稳定性的关键，MSPA(膜稳定蛋白)。目的：本项目的主要目标是确定膜的稳定性对金黄色葡萄球菌抵御免疫攻击和来自鼻部微生物组其他成员的竞争的能力的重要性。竞争：细菌之间存在的竞争策略可以从细菌消耗共享环境中可用的营养的速度，到一种细菌对另一种细菌的直接物理攻击。该项目的这一方面将检查一系列具有不同膜稳定性的金黄色葡萄球菌突变体在与鼻部微生物组的其他成员共同培养时的相对竞争能力。免疫攻击：保护我们免受感染的免疫系统的几个方面集中在攻击细菌的膜以杀死它们。这对我们的微生物组成员提出了一个挑战，他们必须经受住这种攻击。该项目的这一方面将检查一系列具有不同水平膜稳定性的金黄色葡萄球菌突变体抵御人类免疫系统方面的膜攻击的能力。

Background: The human microbiome consists of all of the microorganisms that exist in symbiosis with us on the nonsterile parts of our bodies, including our skin, respiratory tract, digestive tract and genitourinary system. The composition of the microbiome at these sites is key to our health, such that perturbations can increase our susceptibility to many inflammatory and infectious diseases. Despite its importance, our understanding of how bacteria within the microbiome maintain their presence despite the onslaught of our immune system, and in the face of competition from other microorganisms remains unclear. However, one feature that is likely to be key to this is their ability to rapidly sense and respond to environmental changes. As unicellular organisms, this ability of bacteria is entirely reliant on their membrane, and in particular the stability of this membrane as it acts as a platform for all the proteins and molecules that are embedded there that allow it to sense and respond. Model organism: The bacterium Staphylococcus aureus is a member of the nasal and skin microbiome of approximately 30% of the human population. Several molecules have been identified as playing a key role in the membrane stability of S. aureus including its characteristic golden pigment, staphyloxanthin, and a recently identified a small (105 residue) protein that that is key to the stability of the bacterial membrane, MspA (membrane stabilising protein). Aim: The overarching aim of this project is to determine the importance of membrane stability to the ability of S. aureus to withstand both immune attack and competition from other members of the nasal microbiome. Competition: Competitive strategies that exist between bacteria can range from the rate at which the bacteria consume the nutrients available within the shared environment, through to the direct physical attack on one bacterium by another. This aspect of the project will examine the relative competitive abilities of a range of S. aureus mutants with varying levels of membrane stability when co-cultured with other members of the nasal microbiome. Immune attack: Several aspects of our immune system that protects us from infection focus on attacking the membrane of bacteria to kill them. This presents a challenge for members of our microbiome who must withstand this attack. This aspect of the project will examine the ability of a range of S. aureus mutants with varying levels of membrane stability to withstand membrane attack by aspect of the human immune system.