Plasminogen Receptors on C. neoformans
Plasminogen-binding proteins on T. asahii were suggested as described above. As for C. neoformans, a global analysis of plasminogen-binding proteins on the pathogen surface was performed and several candidate proteins were suggested, including heat-shock protein 70, glucose-6 phosphate isomerase, and pyruvate kinase (Stie et al. 2009). However, we also found that neutral polysaccharides containing mannose, galactose, glucose, and xylose were able to bind to human plasminogen and affect its activation. The polysaccharide was determined to be different from GXM, the main component of the capsule. A diverse range of biomolecules, including proteins and carbohydrates, can therefore function as plasminogen receptors and play a role in activation (Ikeda and Ichikawa 2014).
Microbes communicate in animals and in the environment symbiotically, parasitically, or exclusively. Descriptions of the human microbiome survey (Morgan et al. 2013) indicate the significance of microbe-microbe and host-microbe interactions in various diseases including diabetes, psychiatric disorders, and infectious diseases. Insulin action was affected by the gut microbial profile (Serino et al. 2013), and the participation of a gut-microbiome-brain connection in autism spectrum disorder was suggested (Hsiao et al. 2013; Sommer and Backhed 2013).
Figure 16.1 Protein-protein and protein-carbohydrate interactions between microbes and human hosts.
Focusing on the interactions between human pathogenic bacteria and fungi we observed an adherence of S. aureus and C. neoformans, and the resulting C. neoformans death was accompanied by the apoptosis-like characteristics. The molecules determined to contribute to the adherence of these species were triosephosphate isomerase and a-(1 ^ 3) mannooligosaccharides on S. aureus and C. neoformans, respectively. Furthermore, triosephosphate isomerase of S. aureus was able to bind to and activate human plasminogen. Staphylococcal triosephosphate isomerase may therefore be a multifunctional protein that has the ability to communicate with eukaryotes and to play a potential role in tissue adhesion and invasion during the process of infection.
Moreover, additional plasminogen receptors on the yeast pathogen T. asahii have been identified as heparinase and thioredoxin-dependent peroxide reductase. The involvement of moonlighting proteins may therefore have the immense potential to predict microbe and human host protein-protein and protein- carbohydrate interactions (Fig. 16.1; Fatoux-Ardore et al. 2014).