Contributed by Narine Arabyan
Sialidases, also known as neuraminidases, are widely distributed in nature and are found in organisms from Eukarya, Eubacteria, and viruses. Sialidases are glycosyl-hydrolases that cleave the α-ketosidic bond of a terminal sialic acid residue from complex glycans. Sialidases have been implicated and correlated with several diseases. Sialidases play a critical role in microbiology by mediating metabolism, adherence, and infection, and are important regulators of alternate complement pathway activation, red blood cell destruction, cell growth, cell adhesion, and tumor metastasis in mammalian systems1-5. Recently, the importance of sialidases in infection and commensalism, has come to light opening the potential to use newly measured genomic diversity as a means to investigate infection mechanisms.
Sialidase presence is highly correlated with the progress and severity of the disease and the most probable role of sialidase is for successful attachment and colonization. Microbes use sialidases to reveal the cell surface that holds sialic acid-containing cell membrane receptors during infection. Arabyan et al. elucidated how sialidases play an important role by altering the host glycan profiles during infection to gain access of the host epithelial cells by binding to terminal sialic acid receptors to initiate glycan degradation6. Weimer’s group demonstrated that the two sialidases from Salmonella enterica Typhimurium LT2 have the same domains and function as sialidases, however they are structurally very different, indicating domain shuffling and lack of structural conservation6.
Bacterial, viral, and trypanosomal infections of humans and livestock can result in serious medical complications and economic loss. Though antibiotics are available for the treatment of bacterial infections, inhibitors of all sialidases and new drug targets may be medically useful where sialidase activity has been correlated with severe infection pathology. Microbes use sialidases to reveal the cell surface that holds sialic acid-containing cell membrane receptors during infection. In addition to targeting host glycoconjugates, sialidases from Streptococcus pneumonia and Pseudomonas aeruginosa also act as a molecular signal for biofilm formation needed during lung infection. Alternatively, some bacteria (Pseudomonas spp., Haemophilus spp.) use the cleaved sialic acids to sialylate structures on their cell surface, such as flagella, capsule polysaccharide (CPS), or the lipopolysaccharide (LPS), to mask the pathogen from the host immune system. The recent emergence of novel avian A H7N9 influenza virus in poultry and humans in China has shed new light on influenza virus adaptation to mammals using their sialidases. Shi et al. showed that H7N9 appeared to jump the species barrier7. The biological trait required for animal influenza viruses to cross the species barrier is the increased receptor binding specificity for α-2,3sialic acid for avian viruses or α-2,6 sialic acid for human influenza virus8.
1 Walther, T. et al. Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection. PLoS Pathog 9, e1003223, doi:10.1371/journal.ppat.1003223 (2013).
2 Imai, M. & Kawaoka, Y. The role of receptor binding specificity in interspecies transmission of influenza viruses. Curr Opin Virol 2, 160-167, doi:10.1016/j.coviro.2012.03.003 (2012).
3 Varki, A. & Gagneux, P. Multifarious roles of sialic acids in immunity. Ann N Y Acad Sci 1253, 16-36, doi:10.1111/j.1749-6632.2012.06517.x (2012).
4 Chan, R. W. et al. Infection of swine ex vivo tissues with avian viruses including H7N9 and correlation with glycomic analysis. Influenza Other Respir Viruses 7, 1269-1282, doi:10.1111/irv.12144 (2013).
5 de Graaf, M. & Fouchier, R. A. Role of receptor binding specificity in influenza A virus transmission and pathogenesis. EMBO J 33, 823-841, doi:10.1002/embj.201387442 (2014).
6 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).
7 Shi, Y. et al. Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses. Science 342, 243-247, doi:10.1126/science.1242917 (2013).
8 Ichimiya, T., Nishihara, S., Takase-Yoden, S., Kida, H. & Aoki-Kinoshita, K. Frequent glycan structure mining of influenza virus data revealed a sulfated glycan motif that increased viral infection. Bioinformatics 30, 706-711, doi:10.1093/bioinformatics/btt573 (2014).