Variations in gene organization and DNA uptake signal sequence in the folP region between commensal and pathogenic Neisseria species

The upstream region of folP displayed differences in gene order between species, including an insertion of a complete Correia element in Neisseria lactamica and an inversion of a larger genomic segment in Neisseria sicca, Neisseria subflava and Neisseria mucosa. The latter species also had DNA uptake signal sequences (DUS) in this region that were one base different from the DUS in pathogenic Neisseriae. Another interesting finding was evidence of a horizontal transfer event from Neisseria lactamica or Neisseria cinerea that introduced a novel folP allele to the meningococcal population.Genetic recombination events immediately upstream of folP and horizontal transfer have resulted in sequence differences in the folP region between the Neisseria species. This variability could be a consequence of the selective pressure on this region exerted by the use of sulfonamide drugs.Horizontal gene transfer via natural transformation is believed to be the main mechanism to generate genetic diversity among Neisseriae [1-3]. Horizontal transfer has for example contributed to the spread of resistance to penicillin in pathogenic Neisseriae, where the origin of the transforming DNA was traced to commensal Neisseria species [4]. Sulfonamide resistance in some strains of Neisseria meningitidis (the meningococcus) has also been acquired by horizontal transfer [5]. As evidence, a mosaic pattern of fragments with high sequence divergence was detected in the chromosomal folP gene, the sulfonamide resistance determinant. The origin of the transforming DNA is still unknown, but presumable donors are commensal Neisseria species.We have previously demonstrated that commensal Neisseria isolates from healthy carriers exhibit high level sulfonamide resistance, most likely due to sulfonamide-resistant variants of folP [6]. These commensal folP genes differ substantially from previously described folP genes, but the findings suggest that sulfonamide resistance is a property carried among species