Mixed Infection with cagA‐Positive and cagA‐Negative Strains of Helicobacter pylori

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Abstract
Helicobacter pylori infection has been implicated strongly in the pathogenesis of gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, but the reasons for these widely different clinical outcomes are unknown. The aim of this study was to determine whether these differences could be due in part to mixed infection in the same individual, with bacteria having differences in pathogenic factors associated with ulcers. The cagA gene of H. pylori was used to test for mixed infection because it is present in only some strains, and its presence has been associated with ulcers. Polymerase chain reaction (PCR) assays for the cagA gene were applied to H. pylori culture isolates and endoscopic gastric aspirates. Individual bacterial clones were tested for genetic similarity by random primer amplification and restriction endonuclease digestion of urease gene PCR products. The majority of H. pylori-positive patients had strongly cagA-positive culture isolates and endoscopic samples (62.5% and 69.6%, respectively). However, many of these patients had evidence of mixed infection with cagA negative and cagA positive strains in cultures isolates and endoscopic samples (25% and 17.4%, respectively). Mixed infection was found to be due to genetically unrelated strains in two patients in whom genetic analysis was performed. Mixed infection with differences in substrain pathogenic factors might occur in H. pylori infection and might contribute to differences in clinical outcome.