Contributed by Narine Arabyan
Lysozyme hydrolyzes the β-1,4-glycosidic bond of oligosaccharides. These enzymes are part of a broad group of glycosyl hydrolases that are poorly characterized. Lysozyme enzymes belong to the GH24 family of glycosyl hydrolases (GHs)1. GHs play an important role during infection by altering the host glycan structure to gain access of the host epithelial cells by binding to terminal monosaccharides to initiate glycan degradation2. Lysozyme enzymes may be new promising virulence factors due to its β-1,4-glycosidase activity and have the potential to recognize host GlcNAc containing glycans in the form of N-glycans, O-glycans, glycolipids, glycoproteins and glucosaminoglycans during infection3. These GlcNAc molecules are linked to monosaccharides in the glycan via a β-1,4-glycosidic bond4 that can be cleaved by enzymes from Salmonella with lysozyme activity during host association.
Lysozyme enzymes with β-1,4-glycosidase activity are also involved during the secretion of proteins which is central for the virulence of all pathogenic bacteria1. Gram-negative organisms translocate proteins across the peptidoglycan that is composed of linear chains of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) and the alternating sugars are connected by β-1,4-glycosidic bonds5-7. The peptidoglycan structure is a physical barrier for the assembly of macromolecular complexes and for the transport of proteins. For this reason, all bacterial lysozymes degrade the peptidoglycan to allow the assembly of type III or type IV secretion systems essential in virulence, flagella, or conjugation8,9. This remodeling creates gaps in the peptidoglycan necessary for the assembly of these macromolecular systems. Intracellular pathogenic bacteria, such as Brucella abortus, use lysozyme during its early stages of intracellular replication8. Lysozyme enzymes are important for growth and are being recognized as emerging virulence factors.
1 Mushegian, A. R., Fullner, K. J., Koonin, E. V. & Nester, E. W. A family of lysozyme-like virulence factors in bacterial pathogens of plants and animals. Proc Natl Acad Sci U S A 93, 7321-7326 (1996).
2 Arabyan, N. et al. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling. Sci Rep 6, 29525, doi:10.1038/srep29525 (2016).
3 Jacobs, H. et al. Characterization of membrane N-glycan binding sites of lysozyme for cardiac depression in sepsis. Intensive Care Med 31, 129-137, doi:10.1007/s00134-004-2487-y (2005).
4 Stanley, P., Schachter, H. & Taniguchi, N. in Essentials of Glycobiology (eds A. Varki et al.) (2009).
5 Allaoui, A., Sansonetti, P. J. & Parsot, C. MxiD, an outer membrane protein necessary for the secretion of the Shigella flexneri lpa invasins. Mol Microbiol 7, 59-68 (1993).
6 Kirby, A. J. Mechanism and stereoelectronic effects in the lysozyme reaction. CRC Crit Rev Biochem 22, 283-315 (1987).
7 Pei, J. & Grishin, N. V. COG3926 and COG5526: a tale of two new lysozyme-like protein families. Protein Sci 14, 2574-2581, doi:10.1110/ps.051656805 (2005).
8 Del Giudice, M. G., Ugalde, J. E. & Czibener, C. A lysozyme-like protein in Brucella abortus is involved in the early stages of intracellular replication. Infect Immun 81, 956-964, doi:10.1128/IAI.01158-12 (2013).
9 Koraimann, G. Lytic transglycosylases in macromolecular transport systems of Gram-negative bacteria. Cell Mol Life Sci 60, 2371-2388, doi:10.1007/s00018-003-3056-1 (2003).