During an infection, pathogens must quickly adapt to conditions in order to multiply within the body. A research team from the University of Basel in Switzerland has discovered how key proteins switch on machines and Leptospira Pathogens survive and cause disease. This discovery provides new insights into how pathogens regulate their virulence and could open new avenues for therapeutic intervention.
Since the late 20th century, diseases transmitted from animals to humans, so-called zoonoses, have been on the rise. One of these is leptospirosis, an infectious disease that is becoming more common due to climate change. Leptospirosis causes approximately 1 million severe cases and an estimated 60,000 deaths worldwide each year. The disease is a serious public health problem in areas with limited resources, and cases have also occurred in Switzerland.
This disease is caused by a pathogen Leptospira Bacteria. Patients become infected through contact with contaminated water or soil. Without early treatment with antibiotics, the infection can cause organ failure. Once invading the human host, the bacterium switches on virulence factors that allow it to survive and persist within the body. This process is controlled by the protein LvrB, which, when activated, turns bacteria from harmless to harmful.
Switch goes from inactive to active
Until now, it was unclear how exactly this switch protein LvrB functions. In a recent study in Nature Communications, Professor Sebastian Hiller’s team at the University of Basel Biozentrum elucidated the three-dimensional structure and mechanism of action of this protein.
We now understand at the atomic level how molecular switches work and how they are activated. More importantly, we have elucidated the general activation mechanism of this important class of proteins. Our findings will help scientists design drugs that keep LvrB off and prevent pathogens from becoming virulent. ”
Professor Sebastian Hiller, University of Basel
locked and turned off
LvrB is part of a communication system that controls the activity of hundreds of genes associated with bacterial virulence, or the pathogen’s ability to cause disease. “In the off state, LvrB is locked into a symmetric, inactive structure and is unable to activate virulence factors,” explains Elia Agustoni, lead author of the study. “This ‘off’ position prevents bacteria from producing virulence factors unnecessarily, such as when they are outside the body. ”
active and toxic
Host signals activate signal transduction cascades, leading to chemical modifications of LvrB and structural rearrangements. “The conformational change in LvrB breaks its symmetry, thereby activating the protein,” says Agustoni. In the “on” state, LvrB can transmit signals to its partner proteins, which have also been identified by the researchers. Together, they activate virulence genes and Leptospira to spread within the body.
Impact on other infectious diseases
The researchers suggest that interfering with the structural changes that keep LvrB inactive may be a promising strategy to weaken pathogen virulence and prevent infection. This approach could also reduce the risk of antibiotic resistance.
Beyond their relevance to leptospirosis, these mechanistic insights provide a blueprint for understanding the broad class of related signaling systems found throughout bacteria. Many of these belong to pathogens that infect humans, animals, and plants. “Our findings lay the foundation for uncovering many unexplored cellular processes and will support the development of new antibiotics and pesticides,” Hiller emphasizes.
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Reference magazines:
Agustoni, E. others. (2026). Activation mechanism of the full-length histidine kinase LvrB in pathogenic Leptospira spp. Nature Communications. DOI: 10.1038/s41467-026-71783-4. https://www.nature.com/articles/s41467-026-71783-4
