Researchers identified a minimal regulatory module in the plague bacterium Yersinia pestis that coordinates its survival across both flea vectors and mammalian hosts, according to a study published 1 September 2026 in Nature Communications. The team, led by scientists at the University of Lille, CNRS, Inserm, and the Institut Pasteur de Lille, screened flea-induced genes to uncover the regulator HdfR. The factor operates primarily by activating maoP, a gene that encodes a nucleoid-associated protein.
Yersinia pestis relies on this HdfR-MaoP circuit to manage transitions across radically different physiological environments. In the flea vector, the regulatory module drives biofilm-dependent blockage of the insect foregut, a physical state required for transmission. Once exposed to conditions mimicking a mammalian host, the module coordinates baseline changes in the bacterial envelope to prevent complement recognition, while turning on inducible defenses that protect the organism against antimicrobial peptides. Functional testing showed that homologs of HdfR and MaoP are interchangeable, demonstrating that the regulatory architecture is conserved across evolutionary lineages.
Scientists sensitized the bacteria to host defenses by perturbing the HdfR-MaoP pathway with chemical agents. Pharmacological disruption left Y. pestis vulnerable to antimicrobial peptides, exposing the hub as a workable target for intervention. Following the discovery, study authors Alexandre Baillez and Florent Sebbane filed a patent application covering a compound identified during the research that modulates the HdfR-MaoP system.
The European Research Council funded the research under an ERC Synergy grant numbered 101118880, alongside grants ANR-15-CE39-0017 and ANR-21-CE15-0047 from the French National Research Agency. Collaborators from the University of Paris-Saclay, the Institute for Integrative Biology of the Cell, the University of Rouen Normandy, and the Cancer Research Center of Lille assisted with genomic, metabolomic, and antibody analyses. Authors Amélie Dewitte and François Pierre contributed equally to the paper, which Nature Communications accepted on 10 August 2026 following submission on 28 January 2026.
