Abstract To identify adhesion-associated loci, we screened 1500 mutant strains of a Helicobacter pylori mutant library. A mutant that showed decreased adhesion to two gastric epithelial cell lines was identified. Inverse polymerase chain reaction (PCR) revealed that the interrupted locus of this mutant was an hp0015 homolog of H. pylori strain 26695. DNA sequencing and reverse-transcription PCR revealed that hp0015 and two downstream genes ( hp0016 and hp0017) were a transcriptional unit. Deletion and complementation constructs revealed that hp0016 and hp0017 were involved in natural transformation, but not in adhesion. Hp0015 was associated with both adhesion and natural transformation. The reduction of adhesion to human gastric tissues in the hp0015 mutant was similar to that of the babA2 knockout mutants and greater than that of the sabA knockout mutants. Co-culture of a wild-type strain with AGS cells revealed that 19 genes in AGS cells were upregulated; however, five of the 19 genes were not induced by co-culture with hp0015 mutants. These results indicate that hp0015 is associated with adhesion, and hp0015, hp0016, and hp0017 are associated with natural transformation. Hp0017 has been named as virB4/ comB4. Therefore, hp0015 and hp0016 are named as comB2 and comB3, respectively.