Host sialoglycans and bacterial sialidases: a mucosal perspective

Sialic acids are nine‐carbon‐backbone sugars that occupy outermost positions on vertebrate cells and secreted sialoglycoproteins. These negatively charged hydrophilic carbohydrates have a variety of biological, biophysical and immunological functions. Mucosal surfaces and secretions of the mouth, airway, gut and vagina are especially sialoglycan‐rich. Given their prominent positions and important functions, a variety of microbial strategies have targeted host sialic acids for adherence, mimicry and/or degradation. Here we review the roles of bacterial sialidases (neuraminidases) during colonization and pathogenesis of mammalian mucosal surfaces. Evidence is presented to support the myriad roles of mucosal sialoglycans in protecting the host from bacterial infection. In opposition, many bacteria hydrolyse sialic acids during associations with the gastrointestinal, oral, respiratory and reproductive tracts. Sialidases promote bacterial survival in mucosal niche environments in several ways, including: (i) nutritional benefits of sialic acid catabolism, (ii) unmasking of cryptic host ligands used for adherence, (iii) participation in biofilm formation and (iv) modulation of immune function. Bacterial sialidases are among the best‐studied enzymes involved in pathogenesis and may also drive commensal and/or symbiotic host associations. Future studies should continue to define host substrates of bacterial sialidases and the mechanisms of theirpathologic, commensal and symbiotic interactions with the mammalian host.

[1]  R. Dwek,et al.  Secretory IgA N- and O-Glycans Provide a Link between the Innate and Adaptive Immune Systems* , 2003, Journal of Biological Chemistry.

[2]  M. Bäckström,et al.  Composition and functional role of the mucus layers in the intestine , 2011, Cellular and Molecular Life Sciences.

[3]  Liang Tong,et al.  Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production. , 2006, The Journal of clinical investigation.

[4]  L. R. Ruhaak,et al.  Glycosylation of Human Milk Lactoferrin Exhibits Dynamic Changes During Early Lactation Enhancing Its Role in Pathogenic Bacteria-Host Interactions* , 2012, Molecular & Cellular Proteomics.

[5]  J. Brisson,et al.  Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  G Taylor,et al.  Sialidases: structures, biological significance and therapeutic potential. , 1996, Current opinion in structural biology.

[7]  G. Thomas,et al.  The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter , 2009, Proceedings of the National Academy of Sciences.

[8]  Ashu Sharma,et al.  Role of Tannerella forsythia NanH Sialidase in Epithelial Cell Attachment , 2010, Infection and Immunity.

[9]  A. Pshezhetsky,et al.  Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. , 2010, Cellular signalling.

[10]  E. Vimr,et al.  The sialidase superfamily and its spread by horizontal gene transfer , 1993, Molecular microbiology.

[11]  S. Hillier,et al.  Sialidase (neuraminidase) activity among gram-negative anaerobic and capnophilic bacteria , 1990, Journal of clinical microbiology.

[12]  E. Vimr,et al.  Purification and renaturation of membrane neuraminidase from Haemophilus parasuis. , 2003, Veterinary microbiology.

[13]  Ajit Varki,et al.  Siglecs and their roles in the immune system , 2007, Nature Reviews Immunology.

[14]  B. McClane,et al.  Sialidases Affect the Host Cell Adherence and Epsilon Toxin-Induced Cytotoxicity of Clostridium perfringens Type D Strain CN3718 , 2011, PLoS pathogens.

[15]  R. Landmann,et al.  Capnocytophaga canimorsus: A Human Pathogen Feeding at the Surface of Epithelial Cells and Phagocytes , 2008, PLoS pathogens.

[16]  S. King,et al.  Pneumococcal modification of host sugars: a major contributor to colonization of the human airway? , 2010, Molecular oral microbiology.

[17]  V. Nizet,et al.  Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase , 2012, mBio.

[18]  Benjamin P. Westover,et al.  Glycan Foraging in Vivo by an Intestine-Adapted Bacterial Symbiont , 2005, Science.

[19]  M. Malamy,et al.  A role for Bacteroides fragilis neuraminidase in bacterial growth in two model systems , 1993, Infection and Immunity.

[20]  J. Peipert,et al.  Hydrolysis of Secreted Sialoglycoprotein Immunoglobulin A (IgA) in ex Vivo and Biochemical Models of Bacterial Vaginosis* , 2011, The Journal of Biological Chemistry.

[21]  A. Varki,et al.  Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. , 2002, Chemical reviews.

[22]  A. Varki,et al.  Chemical Diversity in the Sialic Acids and Related α-Keto Acids: An Evolutionary Perspective , 2002 .

[23]  D. Beighton,et al.  Utilization of Sialic Acid by Viridans Streptococci , 1996, Journal of dental research.

[24]  K. Achyuthan,et al.  Comparative enzymology, biochemistry and pathophysiology of human exo-alpha-sialidases (neuraminidases). , 2001, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[25]  E. Boyd,et al.  Sialic Acid Catabolism Confers a Competitive Advantage to Pathogenic Vibrio cholerae in the Mouse Intestine , 2009, Infection and Immunity.

[26]  A. Moran,et al.  Sweet-talk: role of host glycosylation in bacterial pathogenesis of the gastrointestinal tract , 2011, Gut.

[27]  Ran Zhang,et al.  Comprehensive characterization of the site-specific N-glycosylation of wild-type and recombinant human lactoferrin expressed in the milk of transgenic cloned cattle. , 2011, Glycobiology.

[28]  B. Weimer,et al.  Bacteroides in the infant gut consume milk oligosaccharides via mucus-utilization pathways. , 2011, Cell host & microbe.

[29]  X. Chen,et al.  An Infant-associated Bacterial Commensal Utilizes Breast Milk Sialyloligosaccharides* , 2011, The Journal of Biological Chemistry.

[30]  Fraser Neuraminidase production by clostridia. , 1978, Journal of medical microbiology.

[31]  Chien-Yu Chen,et al.  Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells , 2011, Proceedings of the National Academy of Sciences.

[32]  Komandoor E. Achyuthan,et al.  Comparative enzymology, biochemistry and pathophysiology of human exo-α-sialidases (neuraminidases) , 2001 .

[33]  S. Hillier,et al.  Sialidases (neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora , 1992, Journal of clinical microbiology.

[34]  Gaynor A Randle,et al.  Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP‐independent periplasmic transporter , 2005, Molecular microbiology.

[35]  G. Taylor,et al.  Structural studies on the Pseudomonas aeruginosa sialidase-like enzyme PA2794 suggest substrate and mechanistic variations. , 2009, Journal of molecular biology.

[36]  G. Hansson,et al.  A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn. , 2009, Glycobiology.

[37]  N. Kawasaki,et al.  Siglecs as sensors of self in innate and adaptive immune responses , 2012, Annals of the New York Academy of Sciences.

[38]  Ajit Varki,et al.  Glycan-based interactions involving vertebrate sialic-acid-recognizing proteins , 2007, Nature.

[39]  David F. Smith,et al.  Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin , 2008, Nature.

[40]  L. Engstrand,et al.  SabA Is the H. pylori Hemagglutinin and Is Polymorphic in Binding to Sialylated Glycans , 2006, PLoS pathogens.

[41]  K. Knobeloch,et al.  Sialylation is essential for early development in mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Wei Zhang,et al.  Deglycosylation of FcalphaR at N58 increases its binding to IgA. , 2010, Glycobiology.

[43]  M. Malamy,et al.  Sialic Acid (N-Acetyl Neuraminic Acid) Utilization by Bacteroides fragilis Requires a Novel N-Acetyl Mannosamine Epimerase , 2009, Journal of bacteriology.

[44]  Jun Liu,et al.  Abrogation of Neuraminidase Reduces Biofilm Formation, Capsule Biosynthesis, and Virulence of Porphyromonas gingivalis , 2011, Infection and Immunity.

[45]  A. Prince,et al.  The NanA Neuraminidase of Streptococcus pneumoniae Is Involved in Biofilm Formation , 2009, Infection and Immunity.

[46]  Philip Sutton,et al.  Mucin dynamics and enteric pathogens , 2011, Nature Reviews Microbiology.

[47]  E. Vimr,et al.  Diversity of Microbial Sialic Acid Metabolism , 2004, Microbiology and Molecular Biology Reviews.

[48]  K. Tsurumi [Sialic acid]. , 1972, Rinsho byori. The Japanese journal of clinical pathology.

[49]  Ashu Sharma,et al.  Role of sialidase in glycoprotein utilization by Tannerella forsythia , 2011, Microbiology.

[50]  J. Ravetch,et al.  A Novel Role for the IgG Fc Glycan: The Anti-inflammatory Activity of Sialylated IgG Fcs , 2010, Journal of Clinical Immunology.

[51]  N. Uldbjerg,et al.  The cervical mucus plug: Structured review of the literature , 2009, Acta obstetricia et gynecologica Scandinavica.

[52]  Yoshio Hirabayashi,et al.  A Cellular Deficiency of Gangliosides Causes Hypersensitivity to Clostridium perfringens Phospholipase C* , 2005, Journal of Biological Chemistry.

[53]  D. Beighton,et al.  Sialidase activity of the "Streptococcus milleri group" and other viridans group streptococci , 1990, Journal of clinical microbiology.

[54]  Mark von Itzstein,et al.  Sialic Acid Recognition by Vibrio cholerae Neuraminidase* , 2004, Journal of Biological Chemistry.

[55]  J. Weiser,et al.  Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae , 2006, Molecular microbiology.

[56]  D. Geddes,et al.  Reduction in the adherence of Pseudomonas aeruginosa to native cystic fibrosis epithelium with anti-asialoGM1 antibody and neuraminidase inhibition. , 1999, The European respiratory journal.