title: The role of ZmpC in the clinical manifestation of invasive pneumococcal disease.
abstract: BACKGROUND
  The clinical severity and course of invasive pneumococcal disease (IPD) differs substantially between patients. Streptococcus pneumoniae harbors large genetic variability. Zinc metalloproteinase C (ZmpC), a secreted pneumococcal protein involved in neutrophil extravasation, inflammation and tissue remodeling, is present in a minority of IPD isolates. We investigated whether the presence of zmpC was associated with the clinical manifestation of IPD.
  
  
  METHODS
  IPD patients admitted to two Dutch hospitals between 2000 and 2013 were included in the study. Detailed clinical data were collected and the serotype and presence of zmpC were determined in the corresponding blood culture isolates.
  
  
  RESULTS
  ZmpC was present in 21% of the 542 included IPD cases and was mainly associated with serotypes 8, 4, 33A/F and 11A/D. Infection with S. pneumoniae positive for zmpC was more frequently observed in females (p=0.048) and patients with a history of smoking (p=0.033). Although no relation to clinical syndrome was observed, zmpC positive cases more often presented with cough, dyspnea and sepsis (p-values 0.026, 0.001 and 0.018), and more frequently required ICU admission (p=0.011) compared to zmpC negative cases.
  
  
  CONCLUSIONS
  The presence of zmpC was associated with a more severe clinical manifestation of IPD. This study demonstrates that information on pneumococcal genetic background may be useful to identify vulnerable individuals, to monitor clinical presentation and to predict the course of IPD.
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands. Electronic address: amelieke.cremers@radboudumc.nl.
authors.forename: Amelieke J H
authors.initials: AJ
authors.lastname: Cremers
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands. Electronic address: ishanakokmeyer@hotmail.com.
authors.forename: Ishana
authors.initials: I
authors.lastname: Kokmeijer
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands. Electronic address: laszlogroh@gmail.com.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Groh
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands. Electronic address: marien.dejonge@radboudumc.nl.
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboudumc, Nijmegen, The Netherlands; Laboratory of Medical Immunology, Department of Laboratory Medicine, Radboudumc, Nijmegen, The Netherlands. Electronic address: gerben.ferwerda@radboudumc.nl.
authors.forename: Gerben
authors.initials: G
authors.lastname: Ferwerda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008666:Metalloendopeptidases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009426:Netherlands; D011008:Pneumococcal Infections / Q000382:microbiology* / Q000473:pathology*; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D037521:Virulence Factors; D008666:Metalloendopeptidases; C478168:ZmpC protein, Streptococcus pneumoniae
keywords: Invasive pneumococcal disease; Streptococcus pneumoniae; Zinc metalloproteinase C