Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori
Abstract
Exchange of genetic information by natural transformation shapes bacterial evolution. In Helicobacter pylori it is thought to drive its unusually high recombination rate, which has a crucial role in the evolution of virulence and the propagation of antibiotics resistance genes. While in most cases uptake of the incoming DNA into the periplasm is mediated by type IV pili, in H. pylori this initial step of natural transformation requires ComB, a unique competence-specific type IV secretion system (T4SS). The mechanisms by which ComB mediates DNA uptake are still poorly understood, since T4SS are usually involved in an opposite process of DNA export. Here, we identify a gene (hp1421) that is absolutely required for uptake of the transforming DNA into the periplasm, although distant from the comB operons. We show that hp1421 codes for a hexameric ATPase from the VirB11 family. HP1421 is present in the cytoplasm and interacts with ComB4, another ATPase of the T4SS inner membrane subcomplex. The structural modelling and functional analysis of HP1421 and its interaction with ComB4 indicate that HP1421 is a missing component of the ComB inner-membrane subcomplex that we propose to name ComB11. Phylogenetic analyses show that comB11 is a H. pylori core gene and suggest that the competence-dedicated ComB T4SS was a recent acquisition within Helicobacteraceae. Hence, co-option of the T4SS for DNA transformation requires nearly all the proteins that were previously essential for DNA conjugation.
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BibTeX
@article{villa2026unveiling,
title = {{Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori}},
author = {J. Francisco Villa and Sumedha Kondekar and Yoann Fauconnet and Mérick Machouri and Céline Lacrouts and Xavier Veaute and Raphaël Guérois and Eduardo P C Rocha and Jessica Andreani and J. Pablo Radicella},
journal = {PLoS Pathogens},
year = {2026},
month = jul,
doi = {10.1371/journal.ppat.1014140},
url = {https://hal.science/hal-05764851v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Unveiling a missing component of the atypical type IV secretion system required for natural transformation of Helicobacter pylori
AU - J. Francisco Villa
AU - Sumedha Kondekar
AU - Yoann Fauconnet
AU - Mérick Machouri
AU - Céline Lacrouts
AU - Xavier Veaute
AU - Raphaël Guérois
AU - Eduardo P C Rocha
AU - Jessica Andreani
AU - J. Pablo Radicella
PY - 2026
DA - 2026/07/14
JO - PLoS Pathogens
DO - 10.1371/journal.ppat.1014140
UR - https://hal.science/hal-05764851v1
AB - Exchange of genetic information by natural transformation shapes bacterial evolution. In Helicobacter pylori it is thought to drive its unusually high recombination rate, which has a crucial role in the evolution of virulence and the propagation of antibiotics resistance genes. While in most cases uptake of the incoming DNA into the periplasm is mediated by type IV pili, in H. pylori this initial step of natural transformation requires ComB, a unique competence-specific type IV secretion system (T4SS). The mechanisms by which ComB mediates DNA uptake are still poorly understood, since T4SS are usually involved in an opposite process of DNA export. Here, we identify a gene (hp1421) that is absolutely required for uptake of the transforming DNA into the periplasm, although distant from the comB operons. We show that hp1421 codes for a hexameric ATPase from the VirB11 family. HP1421 is present in the cytoplasm and interacts with ComB4, another ATPase of the T4SS inner membrane subcomplex. The structural modelling and functional analysis of HP1421 and its interaction with ComB4 indicate that HP1421 is a missing component of the ComB inner-membrane subcomplex that we propose to name ComB11. Phylogenetic analyses show that comB11 is a H. pylori core gene and suggest that the competence-dedicated ComB T4SS was a recent acquisition within Helicobacteraceae. Hence, co-option of the T4SS for DNA transformation requires nearly all the proteins that were previously essential for DNA conjugation.
SN - 1553-7366
SN - 1553-7374
ER -