Background: The signals that drive H. pylori to successfully arrive at a colonization niche in gastric tissue are not understood, but are an essential first step for successful colonization, and ultimately the disease consequences of H. pylori infection. We asked if H. pylori can sense gastric ulceration tissue as a stimulus and tissue site to promote colonization, and if early colonization was dependent on the bacterial chemosensing that control flagellar motility. Aim: In the present study, we asked if H. pylori preferentially colonize ulcerated tissue rather than healthy tissue, and further tested colonization and effects on ulcer healing of isogenic bacterial mutants defective in flagellar rotation (motB) or chemotaxis signal transduction (cheY). Methods: Topical application of acetic acid for 20-30 s to the stomach exterior induced an ulcer in anesthetized C57BL/6 mice. A single gavage of 106 -109 H. pylori was performed 2 days after ulcer induction. Ulcer size and number of bacteria colonizing normal and ulcerated stomach tissues were evaluated at 1 or 7 days after gavage. Results: 1 day after 108 inoculation, motile SS1 H. pylori colonized ulcerated corpus/fundus tissue (41.2 x 104 ± 11.9 x 104 CFU/g tissue) more than corresponding healthy tissue in the same stomachs (4.9 x 104 ± 1.9 x 104 CFU/g tissue, n=8, p,0.05). At 7 days, SS1 delayed ulcer healing (1.9 ± 0.6 mm2 ulcer) vs uninfected controls (0.3 ± 0.1 mm2 ulcer, p,0.05), but colonization was no longer different between healthy and ulcerated tissue. After a reduced inoculum (106), SS1 still preferentially colonized ulcerated tissue at 7 days as measured by CFU cultures (intact: 61.6 x 104 ± 28.2 x 104 CFU/g tissue vs ulcerated: 142.5 x 104 ± 46.2 x 104 CFU/g tissue, p,0.05) and real-time PCR of either 16S RNA/cDNA or the ssa gene as H. pylori markers. motB mutant SS1 H. pylori (106) did not colonize (healthy or ulcerated) tissue or delay ulcer healing. motB mutant SS1 H. pylori (108 -109) colonized in both areas (intact: 767.9 ± 896.6 CFU/g tissue vs ulcerated: 823.8 ± 903.4 CFU/g tissue, no significant different) without affecting ulcer healing. In contrast, H. pylori SS1 lacking cheY (106) was competent to colonize stomach tissue. At 7 days, the cheY mutant had delayed ulcer healing, but did not preferentially colonize ulcerated tissue (intact: 12.5 x 104 ± 12.6 x 104 CFU/g tissue vs ulcerated: 13.1 x 104 ± 6.2 x 104 CFU/g tissue, no significant different). Conclusion: H. pylori can rapidly and preferentially colonize sites of ulceration using chemotactic motility and subsequently slow ulcer repair. Lack of non-specific colonization by motB and cheY mutants suggests injury may release chemoattractants that determine the earliest H. pylori motility toward, and interactions with, host tissue.