Expression and function of secreted proteases in commensal lifestyles of Staphylococci

蛋白酶是一种降解或加工其他蛋白质的蛋白质，在所有形式的生命中都起着重要或基本的作用。蛋白酶也有助于细菌引起疾病的能力。有些细菌是人类微生物群的一部分，它们阻止致病细菌的生长。我们的研究将评估一种相似的分泌蛋白酶的功能和表达差异如何影响两种相关葡萄球菌在人类鼻子上定植的能力。其中，金黄色葡萄球菌只在鼻子上定植，但如果它突破上皮屏障，也会引起严重的感染。相比之下，表皮葡萄球菌也普遍存在于人体皮肤上，但很少引起严重感染。重要的是，表皮葡萄球菌分泌的蛋白酶，被称为Esp，干扰了金黄色葡萄球菌在鼻子上定植的能力。令人惊讶的是，金黄色葡萄球菌能够产生非常相似的蛋白酶。我们认为鼻内的生长条件使表皮葡萄球菌产生这种蛋白酶，从而抑制金黄色葡萄球菌的生长，而同样的环境条件又指示金黄色葡萄球菌不产生这种蛋白酶。我们认为金黄色葡萄球菌只有在进入人体并引起感染时才会产生这种蛋白酶，在那里它不必与表皮葡萄球菌竞争。因此，确定指示这些细菌产生或不产生这种蛋白酶的信号，将使我们更好地了解一些细菌是如何被指示引起疾病的，而另一些细菌是如何对同样的指示作出反应以维持人类健康的。我们将测试每种微生物产生蛋白酶的能力，以响应鼻子或皮肤上可能遇到的信号，包括酸度的变化、游离脂肪酸的存在和寡肽的可用性。帮助细菌对这些信号作出反应的传感蛋白将被识别出来，我们将使这些蛋白失活，以确定细菌如何对它们的丧失作出反应。最后，我们将从每一种细菌中分离出蛋白酶，并修改其性质，以便我们了解它是如何促进表皮葡萄球菌的共栖性，或者反过来阻止金黄色葡萄球菌的定植的。

Proteases are proteins that degrade or process other proteins, and contribute to important or essential functions in all forms of life. Proteases also contribute to the ability of bacteria to cause disease. Some bacteria are part of the human microflora, where they discourage the growth of disease causing bacteria. Our research will evaluate how differences in function and expression of a similar secreted protease contribute to the ability of two related species of Staphylococci to colonize the nose of humans. Of these, Staphylococcus aureus only colonizes the nose, but can also cause severe infections if it breaches the epithelial barrier. In contrast, S. epidermidis is also ubiquitous on human skin, but rarely causes severe infections. Importantly, a secreted protease of S. epidermidis, named Esp interferes with the ability of S. aureus to colonize the nose. Surprisingly, S. aureus is capable of producing a very similar protease. We propose that growth conditions in the nose signal S. epidermidis to produce this protease, to discourage growth of S. aureus, while the same environmental conditions instruct S. aureus not to produce the protease. We believe that S. aureus only produces this protease once it enters the body and causes an infection, where it does not have to compete with S. epidermidis. Consequently, determining the signals that instruct these bacteria to either produce, or not produce this protease, will lead to a better understanding of how some bacteria are instructed to cause disease, and others respond to the same instructions to maintain human health. We will test the ability of each microbe to produce protease in response to signals that may be encountered in the nose or on the skin, including changes in acidity, presence of free fatty acids, and the availability of oligopeptides. Sensor proteins that help the bacteria respond to these signals will be identified, and we will inactivate these proteins to determine how the bacteria respond to their loss. Finally, we will isolate the protease from each bacteria, and modify its properties so that we can understand how it functions to either promote commensalism of S. epidermidis, or alternately to discourage colonization of S. aureus.