title: Hypermutation in pathogenic bacteria: frequent phase variation in meningococci is a phenotypic trait of a specialized mutator biotype.
abstract: 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.
authors.affiliation: Dipartimento di Biologia e Patologia, Cellulare e Molecolare, L. Califano, Università di Napoli Federico II, Centro di Endocrinologia ed Oncologia Sperimentale G. Salvatore of the Consiglio Nazionale delle Ricerche, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Bucci
authors.forename: A
authors.initials: A
authors.lastname: Lavitola
authors.forename: P
authors.initials: P
authors.lastname: Salvatore
authors.forename: L
authors.initials: L
authors.lastname: Del Giudice
authors.forename: D R
authors.initials: DR
authors.lastname: Massardo
authors.forename: C B
authors.initials: CB
authors.lastname: Bruni
authors.forename: P
authors.initials: P
authors.lastname: Alifano
mesh_terms: D000595:Amino Acid Sequence; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D004260:DNA Repair / Q000235:genetics; D004262:DNA Restriction Enzymes / Q000737:chemistry / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000235:genetics* / Q000472:pathogenicity; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D015183:Restriction Mapping; D016415:Sequence Alignment; D012699:Serology; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000737:chemistry / Q000235:genetics*; D014170:Transformation, Genetic
chemical_list: D012333:RNA, Messenger; C058693:Dam methyltransferase; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); D004262:DNA Restriction Enzymes