title: Defining the role of pneumococcal neuraminidases and O-glycosidase in pneumococcal haemolytic uraemic syndrome.
abstract: The host and bacterial factors that lead to development of pneumococcal haemolytic uraemic syndrome (pHUS) remain poorly defined; however, it is widely believed that pneumococcal exposure of the Thomsen-Friedenreich antigen (T-antigen) on host surfaces is a key step in pathogenesis. Two enzymatic activities encoded by pneumococci determine the level of T-antigen exposed. Neuraminidases cleave terminal sialic acid to expose the T-antigen which is subsequently cleaved by O-glycosidase Eng. While a handful of studies have examined the role of neuraminidases in T-antigen exposure, no studies have addressed the potential role of O-glycosidase. This study used 29 pHUS isolates from the USA and 31 serotype-matched controls. All isolates contained eng, and no significant correlation between enzymatic activity and disease state (pHUS and blood non-pHUS isolates) was observed. A prior study from Taiwan suggested that neuraminidase NanC contributes to the development of pHUS. However, we observed no difference in nanC distribution. Similar to previously published data, we found no significant correlation between neuraminidase activity and disease state. Accurate quantification of these enzymatic activities from bacteria grown in whole blood is currently impossible, but we confirmed that there were no significant correlations between disease state and neuraminidase and O-glycosidase transcript levels after incubation in blood. Genomic sequencing of six pHUS isolates did not identify any genetic elements possibly contributing to haemolytic uraemic syndrome. These findings support the hypothesis that while exposure of T-antigen may be an important step in disease pathogenesis, host factors likely play a substantial role in determining which individuals develop haemolytic uraemic syndrome after pneumococcal invasive disease.
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Anirudh K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Amin S
authors.initials: AS
authors.lastname: Osman
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Shireen A
authors.initials: SA
authors.lastname: Woodiga
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: White
authors.affiliation: Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH, USA.|Department of Nephrology, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Mahan
authors.affiliation: Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D002675:Child, Preschool; D005260:Female; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology / Q000503:physiopathology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000378:metabolism*; D011008:Pneumococcal Infections / Q000382:microbiology / Q000503:physiopathology*; D011499:Protein Processing, Post-Translational; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000302:isolation & purification; D014481:United States
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D001426:Bacterial Proteins; C016467:Thomsen-Friedenreich antigen; D006026:Glycoside Hydrolases; D009439:Neuraminidase