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Background  Analysis of the evolutionary dynamics of  Helicobacter pylori  allowed tracing the spread of infection through populations on different continents but transmission pathways between individual humans have not been clearly described.    Materials and Methods  To investigate person-to-person transmission, we studied three families each including one child with persistence of symptoms after antibiotic treatment. Ten isolates from the antrum and corpus of stomach of each family member were analyzed both by sequencing of two housekeeping genes and macroarray tests.    Results  A total of 134 (8.4%) out of the 1590 coding sequences (CDSs) tested, including  cag  PAI and insertion sequences, were present in some but not all isolates (and are therefore defined as variable CDSs). Most of the variable CDSs encoded proteins of unknown function (76/134) or were selfish DNA including that encoding restriction/modification enzymes (13/134). Isolates colonizing the stomach of one individual can vary by point mutations, as seen in  hspA , or by the gain or loss of one to five CDSs. They were considered as (genetic) variants. The phylogenetic clustering of gene profiles obtained on macro-arrays allowed identifying the different strains infecting families. Two to five strains circulated within a family. Identical strains were present in at least two members of all three families supporting the accepted model of intrafamilial transmission. Surprisingly, the mother was not implicated in the transmission of  H. pylori  in the two French families. Sibling-to-sibling transmission and acquisition of  H. pylori  from outside the family appeared to be probable in the transmission pathways.    Conclusion  Macroarray analysis based on previously selected CDSs gives a comprehensive view of the genome diversity of a pathogen. This approach combined with information on the origin of the  hspA  and  glmM  alleles revealed that  Helicobacter pylori  infection may be acquired by more diverse routes than previously expected.

Using Macro-Arrays to Study Routes of Infection of Helicobacter pylori in Three Families