Genetic diversity and stability of the porA allele as a genetic marker in human Campylobacter infection

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.