GAPDH, as a Virulence Factor

Abstract

Pathogens, such as bacteria, viruses, protozoa and fungi, generate molecules that provide them with a selective advantage, often at the expense of the host. These molecules, or virulence factors, enable pathogens to colonize the host through several mechanisms. Some molecules offer the pathogen an advantage through better adhesion to host tissues, or superior invasive capability. Some allow the pathogen to evade or suppress the host's immune system. Some molecules enable intracellular parasites to disable cytoprotective mechansims, by re-directing the host phagocytic vesicles. Many of these molecules are proteins that are exported to the cell's surface or are secreted. As unlikely as it seems, GAPDH appears to play a role as a virulence factor in a number of pathogenic organisms by the mechanisms just described. This highly conserved protein is found on the outer surface or as a secretory product of these organisms. The process by which pathogenic GAPDH, which has >40 % sequence identity to human GAPDH, is exported and attached to the outer surface of cells remains unknown. This chapter also presents a previously unpublished proposed docking sequence on GAPDH. There is also discussion of the potential of using the antigenic properties of pathogenic GAPDH for medical as well as for veterinary purposes.

Anti‐GAPDH Autoantibodies as a Pathogenic Determinant and Potential Biomarker of Neuropsychiatric Diseases

“…A growing body of evidence strongly supports the existence of an altered integrity of the blood–brain barrier in patients with major psychiatric illnesses and NPSLE, resulting in leakage of serum‐derived vascular components into the brain tissue . It is also possible that the autoimmune response to GAPDH is derived from molecular mimicry, since there is evidence of the strong antigenicity of GAPDH expressed on the cell surfaces of bacteria such as group A Streptococcus and Staphylococcus aureus , and fungi such as Candida albicans , during infections .…”

Survey of Surface Proteins from the Pathogenic Mycoplasma hyopneumoniae Strain 7448 Using a Biotin Cell Surface Labeling Approach

“…Pyruvate dehydrogenase, an immunogenic M. hyopneumoniae protein [33], [34], was described as a surface protein involved in the bacterial binding to the host extracellular matrix in Mycoplasma pneumoniae [35]. GAPDH, usually located in the cytoplasm and known to play a central role as a glycolytic enzyme, has been identified on the surface of pathogenic bacteria and was related to pathogenic processes [36], such as adhesion and host matrix binding [37], immunomodulation and immune evasion [38]. L-lactate dehydrogenase, also known as P36, was described as immunogenic for pigs infected with M. hyopneumoniae [39].…”

Comparative proteomic analysis of Xanthomonas citri ssp. citri periplasmic proteins reveals changes in cellular envelope metabolism during in vitro pathogenicity induction

“…Our results suggest, for the first time, that the detection of this enzyme correlates with the induction of known pathogenicity factors (hrp genes). This enzyme has been considered as a virulence factor found on the outer surface or as a secretory product in a number of pathogenic organisms (Aguilera et al, 2012;Seidler, 2013). Furthermore, GAPDH is emerging as one of a group of so-called 'moonlighting' proteins that can exhibit a wide range of biological roles, even in eukaryotic cells (Henderson and Martin, 2014).…”