Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype

Mol Cell. 1999 Apr;3(4):435-45. doi: 10.1016/s1097-2765(00)80471-2.


Expression of serogroup B meningococcal capsular polysaccharide undergoes frequent phase variation involving reversible frameshift mutations within a homopolymeric repeat in the siaD gene. A high rate of phase variation is the consequence of a biochemical defect in methyl-directed mismatch repair. The mutator phenotype is associated to the absence of DNA adenine methyltransferase (Dam) activity in all pathogenic isolates and in 50% of commensal strains. Analysis of the meningococcal dam gene region revealed that in all Dam- strains a gene encoding a putative restriction endonuclease (drg) that cleaves only the methylated DNA sequence 5'-GmeATC-3' replaced the dam gene. Insertional inactivation of the dam and/or drg genes indicated that high rates of phase variation and hypermutator phenotype are caused by absence of a functional dam gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Capsules / genetics
  • Bacterial Capsules / immunology
  • Base Sequence
  • Cloning, Molecular
  • DNA Repair / genetics
  • DNA Restriction Enzymes / chemistry
  • DNA Restriction Enzymes / genetics*
  • Gene Expression Regulation, Bacterial / genetics
  • Genes, Bacterial*
  • Molecular Sequence Data
  • Mutation
  • Neisseria meningitidis / genetics*
  • Neisseria meningitidis / pathogenicity
  • Phenotype
  • RNA, Messenger / analysis
  • Restriction Mapping
  • Sequence Alignment
  • Serology
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / chemistry
  • Site-Specific DNA-Methyltransferase (Adenine-Specific) / genetics*
  • Transformation, Genetic


  • RNA, Messenger
  • Dam methyltransferase
  • Site-Specific DNA-Methyltransferase (Adenine-Specific)
  • DNA Restriction Enzymes

Associated data

  • GENBANK/AF091142
  • GENBANK/AF091143