NATURAL GENETIC EXCHANGE BETWEEN HAEMOPHILUS AND NEISSERIA - INTERGENERIC TRANSFER OF CHROMOSOMAL GENES BETWEEN MAJOR HUMAN PATHOGENS

Members of the bacterial families Haemophilus and Neisseria, important human pathogens that commonly colonize the nasopharynx, are naturally competent for DNA uptake from their environment. In each genus this p rocess is discriminant in favor of its own and against foreign DNA thr ough sequence specificity of DNA receptors, The Haemophilus DNA uptake apparatus binds a 29-bp oligonucleotide domain containing a highly co nserved 9-bp core sequence, whereas the neisserial apparatus binds a 1 0-bp motif, Each motif (''uptake sequence'', US) is highly over-repres ented in the chromosome of the corresponding genus, particularly conce ntrated with core sequences in inverted pairs forming gene terminators . Two Haemophilus core USs were unexpectedly found forming the termina tor of sodC in Neisseria meningitidis (meningococcus), and sequence an alysis strongly suggests that this virulence gene, located next to IS1 106, arose through horizontal transfer from Haemophilus. By using USs as search strings in a computer-based analysis of genome sequence, it was established that while USs of the ''wrong'' genus do not occur com monly in Neisseria or Haemophilus, where they do they are highly likel y to flag domains of chromosomal DNA that have been transferred from H aemophilus. Three independent domains of Haemophilus-like DNA were fou nd in the meningococcal chromosome, associated respectively with the v irulence gene sodC, the bio gene cluster, and an unidentified orf. Thi s report identifies inter-generically transferred DNA and its source i n bacteria, and further identifies transformation with heterologous ch romosomal DNA as a way of establishing potentially important chromosom al mosaicism in these pathogenic bacteria.