Enhanced Fitness of a Helicobacter pylori babA Mutant in a Murine Model

Helicobacter pylori genomes encode over 60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify mutant strains exhibiting differential fitness compared to , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time compared to changes detected in the populations during library passage . The control library proliferated as a relatively stable community , but there was a reduction in the population diversity of this library and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a nonselective bottleneck . We did not identify any OMP mutants exhibiting fitness defects exclusively without corresponding fitness defects . Conversely, a mutant exhibited a strong fitness advantage but not . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.