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BMC Microbiology

, 17:40

Clinical microbiology and vaccines


BackgroundThe 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.

ResultsOne 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, determined that most putative virulence genes could be found in both invasive and carriage phenotypes.

ConclusionsAlthough rare, invasive disease by cnl meningococci may be associated with host immunodeficiency and such patients may benefit from protein-based meningococcal vaccines.

KeywordsCapsule null locus Invasive disease Neisseria meningitidis Africa ST-53 ST-192 AbbreviationsATCCAmerican Type Culture Collection


BIGSdbBacterial Isolate Genome Sequence database

C5Fifth complement component

C6Sixth complement component

C9ninth complement component

ccclonal complex

cgMLSTcore genome MLST

cnlcapsule null locus

COPDChronic obstructive pulmonary disease

cpscapsular polysaccharide synthesis

CSFCerebrospinal fluid


FetAFerric enterochelin receptor

fHbpfactor H-binding protein

GERMS-SAGroup for Enteric, Respiratory and Meningeal Disease Surveillance

HIVHuman immunodeficiency virus

IMDInvasive meningococcal disease

MICMinimum inhibitory concentration

MLSTMultilocus sequence typing

N. meningitidisNeisseria meningitidis

NadANeisserial adhesin A


NHBANeisserial heparin-binding antigen

NICDNational Institute for Communicable Diseases


PCRPolymerase chain reaction

PorAPorin A


rMLSTribosomal multilocus sequence typing


SASouth Africa

STSequence type

TEMTransmission electron microscopy

UKUnited Kingdom

VRVariable region

ΔGene deletion

Electronic supplementary materialThe online version of this article doi:10.1186-s12866-017-0942-5 contains supplementary material, which is available to authorized users.

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Autor: Karistha Ganesh - Mushal Allam - Nicole Wolter - Holly B. Bratcher - Odile B. Harrison - Jay Lucidarme - Ray Borrow - Lin


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