Dancing to Another Tune—Adhesive Moonlighting Proteins in Bacteria

Abstract

Biological moonlighting refers to proteins which express more than one function. Moonlighting proteins occur in pathogenic and commensal as well as in Gram-positive and Gram-negative bacteria. The canonical functions of moonlighting proteins are in essential cellular processes, i.e., glycolysis, protein synthesis, chaperone activity, and nucleic acid stability, and their moonlighting functions include binding to host epithelial and phagocytic cells, subepithelia, cytoskeleton as well as to mucins and circulating proteins of the immune and hemostatic systems. Sequences of the moonlighting proteins do not contain known motifs for surface export or anchoring, and it has remained open whether bacterial moonlighting proteins are actively secreted to the cell wall or whether they are released from traumatized cells and then rebind onto the bacteria. In lactobacilli, ionic interactions with lipoteichoic acids and with cell division sites are important for surface localization of the proteins. Moonlighting proteins represent an abundant class of bacterial adhesins that are part of bacterial interactions with the environment and in responses to environmental changes. Multifunctionality in bacterial surface proteins appears common: the canonical adhesion proteins fimbriae express also nonadhesive functions, whereas the mobility organelles flagella as well as surface proteases express adhesive functions.

Network of Surface-Displayed Glycolytic Enzymes in Mycoplasma pneumoniae and Their Interactions with Human Plasminogen

“…Plg harbors lysine- binding kringle domains (15), which interact with defined sequences of bacterial proteins, as reported for Eno of S. pneumoniae (42,43). However, interaction with Plg was demonstrated not only for enolases but also for other glycolytic enzymes (41). Additionally, Plg binding without the influence of lysine residues was confirmed (25,44).…”

“…The presence of different glycolytic enzymes on the surfaces of a broad range of pathogenic, opportunistic, and commensal bacteria and their involvement not only in metabolic pathways but also in further interactions with the host suggest a common aspect of communication between microbes and the environment (11,14,41). Especially in mycoplasmas, bacteria with reduced genomes, protein multifunction may be a way to use limited genomic resources more effectively to sustain the parasitic lifestyle in defined hosts.…”

“…Among these, Plg is regarded as an important component that influences various factors of the human fibrinolysis system; it is believed to play a part in the dissemination of microorganisms by activation of Plg and the subsequent proteolytic activity of emerging plasmin (15,16). Binding of glycolytic enzymes to Plg seems to be a common aspect since it has been described for many bacterial proteins, including glycolytic enzymes (41). Plg harbors lysine- binding kringle domains (15), which interact with defined sequences of bacterial proteins, as reported for Eno of S. pneumoniae (42,43).…”

The Expanding Landscape of Moonlighting Proteins in Yeasts

“…Mutational studies would be critical to ascertain if the moonlighting umbrella could apply to all proteins that, although usually cytosolic, are also found extracellularly and act in this form to facilitate invasion of the host by pathogenic organisms (13,115). A detailed structural study has been made for the surface enolase of Streptococcus pyogenes and S. pneumoniae.…”

Is it feasible to control pathogen infection by competitive binding of probiotics to the host?

“…The canonical functions of moonlighting proteins attribute to the essential cellular metabolic processes, such as glycolysis, 28 protein synthesis and quality control, 29 and redox homeostasis; 30 however, some of them act as adhesins with a wide variety of affinities for mucin, host cells, carbohydrates, ECM glycoproteins, and plasminogen/plasmin when they emerged on the bacterial cell surface, although the exhibition mechanism remains controversial. 31 ECM in the lamina propria of the GIT is a complex of glycosaminoglycans and ECM glycoproteins, including collagen, fibronectin, laminin, elastin, thrombospondin, tenascin, and nidogen, secreted by epithelial and mesenchymal cells. 32,33 Cells are surrounded by ECM and hence embedded in the tissue, giving physical strength and flexibility, and furthermore, ECM modulates differentiation, migration, polarity, proliferation, and vitality of the cells, by stimulating cell signaling pathways via proteoglycan-cytoskeletal integrin-growth factor receptor axis.…”