From the genome sequence via the proteome to cell physiology - Pathoproteomics and pathophysiology of Staphylococcus aureus

Abstract

While the genome sequence is the blueprint of life, functional genomics is required to transfer the genome sequence to cell physiology. Among the Omics technologies, proteomics holds a privileged position because it deals with the main players of life, the proteins. For the model organism Staphylococcus aureus comprehensive coverage of the proteome was accomplished and used to address physiological and pathophysiological questions. This review article demonstrates that the proteomic view of physiology and pathophysiology of S. aureus unveils cellular processes in an unprecedented manner. These new insights into bacterial adaptation are starting points for detailed follow-up studies aiming at a deep and comprehensive understanding of metabolism, stress responses and virulence of this dangerous pathogen. In vivo proteomics uncovered the life style of S. aureus under infection related conditions, namely after internalization by eukaryotic cells, and in infection settings. However, further analytical advances will improve capabilities for in vivo studies, particularly in murine and human tissue specimen and in this way support the identification of new targets for therapeutic interventions. Furthermore, a comprehensive set of cell surface-associated proteins required for biofilm formation and host cell invasion as well as secreted proteins, among them many proteins of still unknown function, was described. The identification of the functions of these proteins will help to better understand the molecular mechanisms of the different diseases caused by S. aureus, thus leading to a more complete understanding of its pathogenicity. Finally, immunoproteomics can visualize the perception of the pathogen by the immune system and host defense mechanisms and may pave the way to the development of new vaccination approaches, which are urgently required.

Keywords: Cell surface-exposed proteins; Comprehensive proteome coverage; Immunoproteomics; In vivo proteomics; Metabolism; Physiological proteomics; Stress/starvation responses; Virulence factors.