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

Helicobacter pylori (Hp), a Gram-negative bacterial pathogen and aetiologic agent of gastroduodenal disease in humans, is naturally competent for gene tic transformation. Natural competence in bacteria is usually correlated wi th the presence of type IV pili or type IV pilin-like proteins, which are a bsent in Hp. Instead, we recently identified the comB operon in Hp, carryin g four genes tentatively designated as orf2, comB1, comB2 and comB3. We sho w here that all ComB proteins and the 37-amino-acid Orf2 peptide display si gnificant primary sequence and structural homology/identity to the basic co mponents of a type IV secretion apparatus. ComB1, ComB2 and ComB3, now rena med ComB8, ComB9 and ComB10, correspond to the Agrobacterium tumefaciens Vi rB8, VirB9 and VirB10 proteins respectively. The peptide Orf2 carries a lip oprotein motif and a second cysteine residue homologous to VirB7, and was t hus designated ComB7. The putative ATPase ComB4, encoded by the open readin g frame hp0017 of strain 26695, corresponds to virB4 of the A. tumefaciens type IV secretion system. A Hp comB4 transposon insertion mutant was totall y defective in natural transformation. By complementation of a Hp Delta com B deletion mutant, we demonstrate that each of the proteins from ComB8 to C omB10 is absolutely essential for the development of natural transformation competence. The putative lipoprotein ComB7 is not essential, but apparentl y stabilizes the apparatus and modulates the transformation efficiency. Thu s, pathogenic type I Hp strains contain two functional independent type IV transport systems, one for protein translocation encoded by the cag pathoge nicity island and one for uptake of DNA by natural transformation. The latt er system indicates a possible novel mechanism for natural DNA transformati on in bacteria.