title: Genetic mechanisms for loss of encapsulation in polysialyltransferase-gene-positive meningococci isolated from healthy carriers.
abstract: Encapsulated Neisseria meningitidis expressing serogroups A, B, C, W-135, or Y remain a major cause of morbidity and mortality globally. This bacterium is, however, a common commensal inhabitant of the human nasopharynx that causes disease infrequently. Isolates obtained from healthy carriers are frequently unencapsulated and therefore essentially avirulent. The lack of capsule can be due to inactivation of capsule synthesis genes by a variety of genetic mechanisms, or the absence of capsule synthesis genes. Analysis of inactivation mechanisms was undertaken in a diverse but representative set of 166 acapsulate meningococci isolated from carriage that possessed capsule synthesis genes. Slipped strand mispairing in the siaA and siaD genes of the capsule synthesis locus was observed in 39 isolates. Insertion sequence (IS) elements (IS1016-like, IS1106 and IS1301) were responsible for the loss of encapsulation in 46 isolates. Irreversible gene silencing events (insertions, deletions, base exchanges) were found in 47 isolates. Two non-synonymous mutations were identified in close vicinity of the putative active site of the UDP-N-acetylglucosamine 2-epimerase encoded by the siaA gene. The mechanisms for loss of encapsulation were not associated with particular meningococcal genotypes. There was no evidence for successive gene silencing events in the capsule genes, suggesting that the irreversible inactivation events observed were the result of short-term, within-host evolution. These observations are consistent with the postulate that particular meningococcal clonal complexes are associated with possession of a capsule and that this association is important for transmission success.
authors.affiliation: Institute for Hygiene and Microbiology, University of Würzburg, Josef-Schneider-Strasse 2, D-97080 Würzburg, Germany.
authors.forename: Martin V R
authors.initials: MV
authors.lastname: Weber
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.forename: Matthias
authors.initials: M
authors.lastname: Frosch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016667:Bacterial Capsules / Q000096:biosynthesis / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D020137:Base Pair Mismatch; D002238:Carbohydrate Epimerases / Q000235:genetics; D002353:Carrier State / Q000382:microbiology*; D002648:Child; D002675:Child, Preschool; D004251:DNA Transposable Elements / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008589:Meningococcal Infections / Q000382:microbiology*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics* / Q000302:isolation & purification; D010614:Pharynx / Q000382:microbiology; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases; D002238:Carbohydrate Epimerases; C100033:UDP acetylglucosamine-2-epimerase