The rdxA gene of 30 independently isolated Helicobacter pylori strains was sequenced. A comparison of the rdxA sequences revealed a higher percentage of amino acid substitutions in the corresponding protein than in other housekeeping genes. Out of 122 point mutations, 41 were missense and 4 were nonsense. A resistant strain with a nucleotide insertion in the rdxA sequence was also found. With the exception of the point mutations and the insertion generating a stop signal, no particular nucleotide mutation or amino acid substitution could be associated to metronidazole resistance. Moreover, phylogenetic analysis of the 30 nucleotide sequences did not demonstrate specific clusters associated with the resistance phenotype.

The population biology of 78 Helicobacter pylori strains (71 from Swiss Italian, 4 from East Asian and 3 from South African patients) was investigated by sequence analysis of four housekeeping genes : atpD, scoB, glnA and recA. The vacA genotype, the presence of cagA and IS605, the iceA allelic type, and the resistance to metronidazole, clarithromycin and amoxycillin were determined. A high percentage of DNA polymorphic sites (198 % for atpD, 213 % for scoB, 237 % for glnA and 203 % for recA) was found. The phylogenetic trees based on the nucleotide sequences of the four gene fragments showed different topologies and were incongruent. The virulence-associated markers were distributed over the dendrograms and no association was found with phylogenetic clusters or clinical manifestations (chronic gastritis, gastric or duodenal ulcer, MALT lymphoma). Moreover, the H ratios (calculated with the homoplasy test) ranged from 0742 to 0799, depending on the gene fragment examined. All these observations suggest that H. pylori exists as a recombinant population. The clustering of the strains according to their geographical origin (USA/Europe, East Asia, South Africa) that has recently been demonstrated elsewhere could only be confirmed for the East Asian vacA s1c strains. In contrast, the South African strains clustered together only in the atpD tree. Presumably, recombination at the different loci has masked the evolutionary relationship among the strains. Keywords : H. pylori, housekeeping genes, antibiotic resistance INTRODUCTIONHelicobacter pylori is a microaerophilic, Gram-negative, slow-growing, spiral-shaped and flagellate microorganism. Its ecological niche is the human gastric mucosa, where it can survive in an acid environment thanks to a powerful urease activity (Blaser, 1997). The bacterium, discovered in 1983 by Robin Warren and Barry Marshall, has been associated with various gastropathologies such as chronic atrophic gastritis, Abbreviation :MALT lymphoma, gastric mucosa-associated lymphoid tissue lymphoma.The GenBank accession numbers for the sequences reported in this paper are AY004351-AY004662 peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) Roggero et al., 1995). Once acquired, H. pylori usually persists for life, unless eradicated by antimicrobial therapy. Even though the prevalence of infection may be very high (70-90 % in developing countries, 25-50 % in developed countries), most humans infected with H. pylori are asymptomatic and only a few patients develop peptic ulcer or gastric cancer (Pounder, 1995). Host genetic predisposition and local environmental factors, together with bacterial genotypes, may play an important role in the development of disease.Since H. pylori is involved in gastric pathology, researchers have tried to identify specific virulence No 186A MALT S S s1b-m1 Yes A2 No 18A CG R R s1a-m1 Yes A2 Yes 192A DU S S s1a-m1 Yes A2 Yes 22A CG S S s1a-m1 Yes A1 No 24C CG S S s2-m2a Yes A2 No 25A DU ...