title: Genetic diversity and stability of the porA allele as a genetic marker in human Campylobacter infection.
abstract: The major outer-membrane protein (MOMP) of Campylobacter jejuni and Campylobacter coli, encoded by the porA gene, is extremely genetically diverse. Conformational MOMP epitopes are important in host immunity, and variation in surface-exposed regions probably occurs as a result of positive immune selection during infection. porA diversity has been exploited in genotyping studies using highly discriminatory nucleotide sequences to identify potentially epidemiologically linked cases of human campylobacteriosis. To understand the overall nature and extent of porA diversity and stability in C. jejuni and C. coli we investigated sequences in isolates (n=584) obtained from a defined human population (approx. 600,000) over a defined time period (1 year). A total of 196 distinct porA variants were identified. Regions encoding putative extracellular loops were the most variable in both nucleotide sequence and length. Phylogenetic analysis identified three porA allele clusters that originated in (i) predominantly C. jejuni and a few C. coli, (ii) solely C. jejuni or (iii) predominantly C. coli and a few C. jejuni. The stability of porA within an individual human host was investigated using isolates cultured longitudinally from 64 sporadic cases, 27 of which had prolonged infection lasting between 5 and 98 days (the remainder having illness of normal duration, 0-4 days), and 20 cases from family outbreaks. Evidence of mutation was detected in two patients with prolonged illness. Despite demonstrable positive immune selection in these two unusual cases, the persistence of numerous variants within the population indicated that the porA allele is a valuable tool for use in extended typing schemes.
authors.affiliation: The Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Cody
authors.affiliation: The Tinbergen Building, Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, UK.
authors.forename: M J C
authors.initials: MJC
authors.lastname: Maiden
authors.affiliation: National Institute for Health Research, Oxford Biomedical Research Centre Programme, John Radcliffe Hospital, Oxford OX3 9DU, UK.|Nuffield Department of Clinical Laboratory Sciences, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Dingle
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D015373:Bacterial Typing Techniques / Q000379:methods; D002169:Campylobacter Infections / Q000453:epidemiology / Q000382:microbiology*; D017000:Campylobacter coli / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D016123:Campylobacter jejuni / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D005798:Genes, Bacterial; D005819:Genetic Markers; D014644:Genetic Variation; D042822:Genomic Instability; D006801:Humans; D008137:Longitudinal Studies; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D018272:Porins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D005819:Genetic Markers; D018272:Porins; C095080:major outer membrane protein, Campylobacter jejuni