SummaryGenetic recombination can be important evolutionarily in speeding the adaptation of organisms to new environments and in purging deleterious mutations. Here, we describe polymerase chain reaction (PCR), hybridization and DNA sequence-based evidence of six such exchanges between two strains of Helicobacter pylori during natural mixed infection of a patient in Lithuania. One parent strain contained the 37 kb long, virulence-associated cag pathogenicity island (PAI), and the other strain lacked this PAI. Most H. pylori from the patient had descended from the cag þ parent, but had become cag ¹ during infection. This had resulted from transfer of DNA containing the 'empty site' allele from the cag ¹ strain and homologous recombination, not from excision of the cag PAI without DNA transfer. Other cases of recombination involved genes for an outer membrane protein (omp5 and omp29; also called HP0227 and HP1342) and a putative phosphoenolpyruvate synthase (ppsA ; HP0121). Replacement of a short patch of DNA sequence (36-124 bp) was also seen. As the chance of forming any given recombinant is small, the abundance of recombinants in this patient suggests selection for particular recombinant genotypes during years of chronic infection. We suggest that genetic exchange among unrelated H. pylori strains, as documented here, is important because of the diversity of this gastric pathogen and its human hosts. Certain H. pylori recombinants may grow better in a given host than either parent. The vigour of growth, in turn, could impact on the severity of disease that infection can elicit.

Here we describe ISHp609 of Helicobacter pylori, a new member of the IS605 mobile element family that is novel and contains two genes whose functions are unknown, jhp960 and jhp961, in addition to homologs of two other H. pylori insertion sequence (IS) element genes, orfA, which encodes a putative serine recombinasetransposase, and orfB, whose homologs in other species are also often annotated as genes that encode transposases. The complete four-gene element was found in 10 to 40% of strains obtained from Africa, India, Europe, and the Americas but in only 1% of East Asian strains. Sequence comparison of 10 representative ISHp609 elements revealed higher levels of DNA sequence matches (99%) than those seen in normal chromosomal genes (88 to 98%) or in other IS elements (95 to 97% for IS605, IS606, and IS607) from the same H. pylori populations. Sequence analysis suggested that ISHp609 can insert at many genomic sites with its left end preferentially next to TAT, with no target specificity for its right end, and without duplicating or deleting target sequences. A deleted form of ISHp609, containing just jhp960 and jhp961 and 37 bp of orfA, found in reference strain J99, was at the same chromosomal site in 15 to 40% of the strains from many geographic regions but again in only 1% of the East Asian strains. The abundance and sequence homogeneity of ISHp609 and of this nonmobile remnant suggested a recent bottleneck and then rapid spread in H. pylori populations, possibly selected by the contributions of the elements to bacterial fitness.Insertion sequence (IS) elements are a diverse group of specialized DNA segments that move to new sites in prokaryotic and eukaryotic genomes by mechanisms that do not require extensive DNA sequence homology (for reviews see references 5, 7, and 19). They cause insertion mutations and genome rearrangements, affect nearby gene expression, and help mediate the spread of resistance and virulence determinants within and among species. Many IS elements specify just a single transposase protein that acts in concert with host proteins at each end of the element to mediate insertion. Other, more complex elements, such as Tn7, specify two or more proteins that act together as the transposase, plus additional proteins that help select insertion sites or affect the efficiency of transposition. Host proteins can also affect the frequency or specificity of transposition of certain elements. Many, but not all, species of elements terminate in short inverted repeats (size range, 9 to 40 bp) and generate short direct repeats of target sequences (typically 2 to 9 bp) when they transpose.Each of the four known species of IS elements in H. pylori (IS605, IS606, IS607, and ISHp608) belongs to the distinctive IS605 mobile element family, and each seems to be chimeric, containing two transposition-related genes, orfA and orfB, that may have different phylogenetic origins (12,14,16). The IS605 element family is divisible into two subfamilies based on orfA homologies; in one subfamily, represented by IS607...