title: Molecular characterization of invasive capsule null Neisseria meningitidis in South Africa.
abstract: BACKGROUND
  The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear. We identified four invasive cnl meningococci through laboratory-based surveillance in South Africa from 2003 through 2013, which we aimed to characterize using whole genome data.
  
  
  RESULTS
  One isolate [NG: P1.7-2,30: F1-2: ST-53 (cc53)] contained cnl allele 12, and caused empyema in an adult male with bronchiectasis from tuberculosis, diabetes mellitus and a smoking history. Three isolates were NG: P1.18-11,42-2: FΔ: ST-192 (cc192) and contained cnl allele 2. One patient was an adolescent male with meningitis. The remaining two isolates were from recurrent disease episodes (8 months apart) in a male child with deficiency of the sixth complement component, and with the exception of two single nucleotide polymorphisms, contained identical core genomes. The ST-53 (cc53) isolate possessed alleles for NHBA peptide 191 and fHbp variant 2; whilst the ST-192 (cc192) isolates contained NHBA peptide 704 and fHbp variant 3. All four isolates lacked nadA. Comparison of the South African genomes to 61 additional cnl genomes on the PubMLST Neisseria database ( http://pubmlst.org/neisseria/ ), determined that most putative virulence genes could be found in both invasive and carriage phenotypes.
  
  
  CONCLUSIONS
  Although rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. karisthag@nicd.ac.za.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. karisthag@nicd.ac.za.
authors.forename: Karistha
authors.initials: K
authors.lastname: Ganesh
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
authors.forename: Mushal
authors.initials: M
authors.lastname: Allam
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wolter
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Holly B
authors.initials: HB
authors.lastname: Bratcher
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Odile B
authors.initials: OB
authors.lastname: Harrison
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Lucidarme
authors.affiliation: Meningococcal Reference Unit, Public Health England, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
authors.forename: Linda
authors.initials: L
authors.lastname: de Gouveia
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
authors.forename: Susan
authors.initials: S
authors.lastname: Meiring
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
authors.forename: Monica
authors.initials: M
authors.lastname: Birkhead
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anne
authors.initials: A
authors.lastname: von Gottberg
authors.affiliation: National Institute for Communicable Diseases (NICD), A division of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.|School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Mignon
authors.initials: M
authors.lastname: du Plessis
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics; D000293:Adolescent; D000483:Alleles; D000942:Antigens, Bacterial / Q000235:genetics; D016667:Bacterial Capsules / Q000235:genetics*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D001987:Bronchiectasis / Q000150:complications; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D048909:Diabetes Complications; D003920:Diabetes Mellitus; D004653:Empyema / Q000382:microbiology; D005798:Genes, Bacterial / Q000235:genetics*; D056426:Genetic Loci; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008585:Meningitis, Meningococcal / Q000453:epidemiology; D008589:Meningococcal Infections / Q000453:epidemiology / Q000382:microbiology*; D022401:Meningococcal Vaccines / Q000276:immunology; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D009345:Neisseria meningitidis / Q000166:cytology / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D010641:Phenotype; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012907:Smoking; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000150:complications; D014774:Virulence / Q000235:genetics; D055815:Young Adult
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D005819:Genetic Markers; D022401:Meningococcal Vaccines; C000620214:NHBA protein, Neisseria meningitidis; C501982:NadA protein, Neisseria meningitidis; C484699:factor H-binding protein, Neisseria meningitidis
keywords: Africa; Capsule null locus; Invasive disease; Neisseria meningitidis; ST-192; ST-53