A dual-host regulatory hub integrating biofilm formation and innate immunity resistance

Abstract

Vector-borne pathogens must adapt to sharply distinct host environments, yet the regulatory logic that coordinates transitions between opposing host-specific programs remains poorly defined. Here, we identify a minimal regulatory module in the flea-borne pathogen Yersinia pestis that integrates vector transmission with resistance to mammalian innate immunity. Screening of flea-induced genes uncovered the regulator HdfR, which acts primarily through activation of maoP , encoding a nucleoid-associated protein. This HdfR-MaoP module promotes biofilm-dependent foregut blockage in the flea while coordinating baseline envelope adaptations that limit complement recognition and inducible responses that confer resistance to antimicrobial peptides under mammalian host-like conditions. Functional interchangeability of HdfR and MaoP homologs reveals evolutionary conservation of this regulatory logic, and pharmacological perturbation of the module sensitizes Y. pestis to antimicrobial peptides. Together, these findings define a parsimonious and evolutionarily conserved regulatory hub that orchestrates bacterial success across abrupt environmental transitions and exposes a tractable point of intervention.

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Cite

BibTeX RIS

BibTeX

@article{baillez2026dualhost,
  title = {{A dual-host regulatory hub integrating biofilm formation and innate immunity resistance}},
  author = {Alexandre Baillez and Amélie Dewitte and François Pierre and Mounia Kortebi and Virginia S Lioy and Mélanie Hillion and Julie Hardouin and Sébastien Janel and Xavier Thuru and Charlotte Clarisse and Hassiba Bouafia and Catherine Robbe Masselot and Sébastien Bontemps-Gallo and Florent Sebbane},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77307-4},
  url = {https://hal.science/hal-05734102v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - A dual-host regulatory hub integrating biofilm formation and innate immunity resistance
AU  - Alexandre Baillez
AU  - Amélie Dewitte
AU  - François Pierre
AU  - Mounia Kortebi
AU  - Virginia S Lioy
AU  - Mélanie Hillion
AU  - Julie Hardouin
AU  - Sébastien Janel
AU  - Xavier Thuru
AU  - Charlotte Clarisse
AU  - Hassiba Bouafia
AU  - Catherine Robbe Masselot
AU  - Sébastien Bontemps-Gallo
AU  - Florent Sebbane
PY  - 2026
DA  - 2026/09/01
JO  - Nature Communications
DO  - 10.1038/s41467-026-77307-4
UR  - https://hal.science/hal-05734102v1
AB  - Vector-borne pathogens must adapt to sharply distinct host environments, yet the regulatory logic that coordinates transitions between opposing host-specific programs remains poorly defined. Here, we identify a minimal regulatory module in the flea-borne pathogen Yersinia pestis that integrates vector transmission with resistance to mammalian innate immunity. Screening of flea-induced genes uncovered the regulator HdfR, which acts primarily through activation of maoP , encoding a nucleoid-associated protein. This HdfR-MaoP module promotes biofilm-dependent foregut blockage in the flea while coordinating baseline envelope adaptations that limit complement recognition and inducible responses that confer resistance to antimicrobial peptides under mammalian host-like conditions. Functional interchangeability of HdfR and MaoP homologs reveals evolutionary conservation of this regulatory logic, and pharmacological perturbation of the module sensitizes Y. pestis to antimicrobial peptides. Together, these findings define a parsimonious and evolutionarily conserved regulatory hub that orchestrates bacterial success across abrupt environmental transitions and exposes a tractable point of intervention.
SN  - 2041-1723
SN  - 2041-1723
ER  -

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