Rapid genetic analysis of Helicobacter pylori gastric mucosal colonization in suckling mice

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Abstract
Previously described animal models for Helicobacter pylori infection have been limited by cumbersome host requirements (e.g., germ-free conditions or unusual species) or are applicable to only special subsets of H. pylori strains (e.g., fresh clinical isolates or animal-adapted derivatives). Here, we report that 5- to 6-day-old outbred CD-1 (ICR) suckling mice support 24-h colonization of all H. pylori strains tested (SS1, 26695 SmR-1, 43504 SmR-1, and G27 SmR-1), including lab-passaged strains that cannot be adapted for colonization of adult animals. Total colony-forming units (cfu) recovered from infection with lab-passaged strains did not differ from those with mouse-adapted SS1. We also tested this model's ability to detect colonization defects in strains carrying mutations in known virulence genes by coinfecting with wild-type H. pylori and measuring differential recovery. This competition assay identified colonization defects in several classes of known attenuated mutants, including those defective in acid resistance ( ureA ), metabolism ( frdA ), motility ( motB ), and chemotaxis ( cheY ). A mutant defective in copA (copper transporting P-type ATPase) is nonattenuated in adult and infant mice. Possibly because of the limited duration of infection, our model did not identify defects in vacuolating cytotoxin ( vacA ) or γ-glutamyltranspeptidase ( ggt ) as attenuating, in contrast to results from other animal models. We also identified a new virulence gene (HP0507) encoding a conserved hypothetical protein, which is important for colonization in our model. The suckling mouse model offers a rapid method to identify colonization defects in any H. pylori strain and may have utility as a new tool for studying immunity to primary infection.