Bacterial proteomics and its role in antibacterial drug discovery

Gene-expression profiling technologies in general, and proteomic technologies in particular have proven extremely useful to study the physiological response of bacterial cells to various environmental stress conditions. Complex protein toolkits coordinated by sophisticated regulatory networks have evolved to accommodate bacterial survival under ever-present stress conditions such as varying temperatures, nutrient availability, or antibiotics produced by other microorganisms that compete for habitat. In the last decades, application of man-made antibacterial agents resulted in additional bacterial exposure to antibiotic stress. Whereas the targeted use of antibiotics has remarkably reduced human suffering from infectious diseases, the ever-increasing emergence of bacteria that are resistant to antibiotics has led to an urgent need for novel antibiotic strategies. The intent of this review is to present an overview of the major achievements of proteomic approaches to study adaptation networks that are crucial for bacterial survival with a special emphasis on the stress induced by antibiotic treatment. A further focus will be the review of the, so far few, published efforts to exploit the knowledge derived from bacterial proteomic studies directly for the antibacterial drug-discovery process. (c) 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:549-565, 2005.