Natural transformation competence in <i>Helicobacter pylori</i> is mediated by the basic components of a type IV secretion system

<jats:p> <jats:italic>Helicobacter pylori</jats:italic> (<jats:italic>Hp</jats:italic>), a Gram‐negative bacterial pathogen and aetiologic agent of gastroduodenal disease in humans, is naturally competent for genetic transformation. Natural competence in bacteria is usually correlated with the presence of type IV pili or type IV pilin‐like proteins, which are absent in <jats:italic>Hp</jats:italic>. Instead, we recently identified the <jats:italic>comB</jats:italic> operon in <jats:italic>Hp</jats:italic>, carrying four genes tentatively designated as <jats:italic>orf2</jats:italic>, <jats:italic>comB1</jats:italic>, <jats:italic>comB2</jats:italic> and <jats:italic>comB3</jats:italic>. We show here that all ComB proteins and the 37‐amino‐acid Orf2 peptide display significant primary sequence and structural homology/identity to the basic components of a type IV secretion apparatus. ComB1, ComB2 and ComB3, now renamed ComB8, ComB9 and ComB10, correspond to the <jats:italic>Agrobacterium tumefaciens</jats:italic> VirB8, VirB9 and VirB10 proteins respectively. The peptide Orf2 carries a lipoprotein motif and a second cysteine residue homologous to VirB7, and was thus designated ComB7. The putative ATPase ComB4, encoded by the open reading frame <jats:italic>hp0017 of</jats:italic> strain 26695, corresponds to <jats:italic>virB4</jats:italic> of the <jats:italic>A. tumefaciens</jats:italic> type IV secretion system. A <jats:italic>Hp comB4</jats:italic> transposon insertion mutant was totally defective in natural transformation. By complementation of a <jats:italic>Hp</jats:italic>Δ<jats:italic>comB</jats:italic> deletion mutant, we demonstrate that each of the proteins from ComB8 to ComB10 is absolutely essential for the development of natural transformation competence. The putative lipoprotein ComB7 is not essential, but apparently stabilizes the apparatus and modulates the transformation efficiency. Thus, pathogenic type I <jats:italic>Hp</jats:italic> strains contain two functional independent type IV transport systems, one for protein translocation encoded by the <jats:italic>cag</jats:italic> pathogenicity island and one for uptake of DNA by natural transformation. The latter system indicates a possible novel mechanism for natural DNA transformation in bacteria.</jats:p>