Cell-Surface Enolase: A Complex Virulence Factor
Impact of Streptococcal Enolase in Virulence
Marcus Fulde1,2 and Simone Bergmann3
- 1 Department of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
- 2 Present address: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie Universitat Berlin, Berlin, Germany
- 3 Department of Infection Biology, Institute of Microbiology, Technische Universitat Braunschweig, Braunschweig, Germany
Enolases represent typical examples of moonlighting proteins, exhibiting multiple functions as a consequence of changes in cellular localization, cell type, oligomeric state, or the cellular concentration of a ligand, substrate, cofactor, or product (Jeffery 1999). Usually these proteins are produced in the cytoplasm and act as key glycolytic enzymes of the Embden Mayerhoff Parnas catabolic pathway and the first step of gluconeogenesis (Wold et al. 1971). Biochemically, enolases display hydrolyzing activity, thereby reversibly converting 2-phospho glycerate (2-PG) to phosphoenol pyruvate (PEP).
Although first mentioned as early as in 1934 (Lohmann and Meyerhof 1934), surface localization as well as the plasminogen-binding activity of eukaryotic enolase was not described fully until around 60 years later (Miles et al. 1991). The first experimental evidence characterizing the streptococcal enolase as a moonlighting protein took an additional seven years, and was not published until 1998 (Pancholi and Fischetti 1998). As key metabolic enzymes, enolases are widely distributed among all branches of life including archaea, bacteria, and eukaryotes (Wold et al. 1971). During the last decade, the amount of publications presenting additional functions of surface-displayed streptococcal enolases has increased massively and led to the definition of enolase as a protein with multiple functions.
This chapter provides an overview of the diversity of streptococcal enolases in virulence (Fig. 13.1). Interaction with the host's extracellular matrix, but also adhesion to and invasion of eukaryotic cells, is discussed.
Moonlighting Proteins: Novel Virulence Factors in Bacterial Infections, First Edition. Edited by Brian Henderson.
© 2017 John Wiley & Sons, Inc. Published 2017 by John Wiley & Sons, Inc.
Figure 13.1 Scheme of moonlighting functions of streptococcal enolase in four categories: interaction with fibrinolysis; stress response; intracellular activities; and function as adhesion cofactor. Enolase structure source: Ehinger et al. (2004). Reproduced with kind permission of Elsevier.