title: Sequence variation and conservation in virulence-related genes of Bordetella pertussis isolates from the UK.
abstract: To determine the value of gene markers for surveillance and to assess the genetic stability of potential acellular pertussis vaccine components, the sequence variation in ten virulence-related genes of Bordetella pertussis was investigated in strains isolated in the UK between 1920 and 2002. These genes encode: pertactin (prnA); pertussis toxin subunits S1 (ptxA) and S3 (ptxC); tracheal colonization factor (tcfA); bordetella autotransporter protein C (bapC); bordetella resistance to killing protein (brkA); fimbrial antigen 2 (fim2); outer-membrane protein Q (ompQ); virulence-activated gene 8 (vag8) and adenylate cyclase toxin (cyaA). The encoded proteins are either components of current acellular vaccines (ACVs), or potential virulence markers for B. pertussis. Three strains used in the pertussis UK whole-cell vaccine (WCV), strain Tohama-I used for production of ACV components and the type strain of B. pertussis (18323(T)) were also analysed. Several novel alleles were found. The UK isolates were assigned multi-locus sequence types (MLSTs) according to a previously described scheme for B. pertussis based on three of these genes (ptxA, ptxC and tcfA). Compared with isolates from other countries, the UK clinical strains showed a distinct distribution of MLSTs. Apart from one strain that was MLST-3, all other recent isolates (2000-2002) were identified as MLST-5. These isolates differed from the three WCV strains, which were MLST-2 or MLST-3, the Tohama-I strain (MLST-2) and the type strain of B. pertussis (MLST-9). MLST-3 and MLST-5 differ only by a single synonymous mutation, but this method does indicate that currently circulating strains of B. pertussis are not identical to the vaccine types, and they may differ in other important characteristics. Two new MLSTs were identified amongst historical UK isolates. Sequence-based typing offers a convenient method of analysing and comparing populations of B. pertussis from different time periods and from different countries. The variation exhibited by prnA and fim2 suggests that they could be useful, additional epidemiological markers in such a typing scheme.
authors.affiliation: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK 2Health Protection Agency, Respiratory and Systemic Infection Laboratory, Specialist and Reference Microbiology Division, 61 Colindale Avenue, London NW9 5HT, UK.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Packard
authors.affiliation: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK 2Health Protection Agency, Respiratory and Systemic Infection Laboratory, Specialist and Reference Microbiology Division, 61 Colindale Avenue, London NW9 5HT, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Parton
authors.affiliation: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK 2Health Protection Agency, Respiratory and Systemic Infection Laboratory, Specialist and Reference Microbiology Division, 61 Colindale Avenue, London NW9 5HT, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Coote
authors.affiliation: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, UK 2Health Protection Agency, Respiratory and Systemic Infection Laboratory, Specialist and Reference Microbiology Division, 61 Colindale Avenue, London NW9 5HT, UK.
authors.forename: Norman K
authors.initials: NK
authors.lastname: Fry
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015373:Bacterial Typing Techniques; D001483:Base Sequence; D001886:Bordetella pertussis / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D017124:Conserved Sequence; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D010567:Pertussis Vaccine; D017422:Sequence Analysis, DNA; D006113:United Kingdom / Q000453:epidemiology; D014774:Virulence / Q000235:genetics; D014917:Whooping Cough / Q000453:epidemiology / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D010567:Pertussis Vaccine