Grant: Discovery Grants Program - Individual

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.