Nitrosative stress in enterobacteria - the S-nitrosoproteome and an assessment of cellular protective functions in vitro and in vivo

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Molecules that are important in biology include not only familiar organic macromolecules (nucleic acids, proteins, fats, carbohydrates) but also small inorganic molecules or ions. One of the most important of these, and the most topical, is nitrogen monoxide (nitric oxide, NO). This gas is produced by animals, plants and microbes and is also generated chemically in many environments. NO is potentially toxic to microbes, which must defend themselves from its chemical reactivity. The current interest in NO by research scientists arises from the fact that it is an important signaling molecule in animals and plants, involved in controlling blood vessel relaxation, nerve function and immunity. In addition, NO reacts with macromolecules, modifying their function with important biological implications. These processes (called nitrosation, nitrosylation, nitration), in which the NO group is covalently bound to the macromolecule, are highly selective and so we cannot predict which proteins will be modified. This research project sets out to measure the extent of these reactions inside intact bacteria. We wish also to test the idea that the defences used by bacteria against NO and related chemicals lead to a reduction in protein modification by NO. Finally, we wish to see whether bacteria that have been engulfed by white blood cells are prone to these modifications and whether the bacterial defence mechanisms limit these reactions. Overall, these experiments will help us to understand which molecules within bacteria are susceptible to NO attack and whether Man's antimicrobial strategies might benefit from this knowledge.