How pathogens switch to "dangerous"
Advertisement
During an infection, pathogens quickly adapt to the conditions in the body in order to survive. A research team at the University of Basel has now discovered how a protein switches on the machinery in the pathogen Leptospira that helps it survive in the body and cause disease. The work provides previously unknown insights into how pathogens control their virulence and opens up new starting points for therapies.
Since the end of the last century, diseases that pass from animals to humans, known as zoonoses, have been on the rise. Leptospirosis is one zoonosis that is becoming increasingly common as a result of climate change. It causes around one million serious cases of the disease worldwide every year, killing an estimated 60,000 people. This disease is a serious health problem, particularly in areas with scarce resources, but cases are also occurring in Switzerland.
Leptospirosis is caused by Leptospira bacteria. People become infected mainly through contaminated water and soil. If the infection is not treated early with antibiotics, it can lead to life-threatening organ failure. When it enters the body, the pathogen activates so-called virulence factors in order to survive. This is controlled by the protein LvrB: only when it is active can the bacteria develop their pathogenic potential.
Symbol image
AI-generated image
From inactive to active
Until now, it was unclear exactly how LvrB is activated. In a study recently published in "Nature Communications", Prof. Sebastian Hiller's team at the Biozentrum of the University of Basel has now been able to elucidate the three-dimensional structure of the protein and its exact mode of action.
"We now understand at the atomic level how this molecular switch works, i.e. how it is switched on. And more importantly, we have discovered a general activation mechanism that affects a large number of other bacterial proteins," says Hiller. "Our findings are also important for the development of active substances. If we succeed in permanently switching off LvrB, we could prevent the pathogen from switching to virulent, i.e. dangerous, in the body."
Blocked and inactive
LvrB is part of a communication system that regulates the activity of hundreds of genes associated with the virulence of the pathogen - i.e. its ability to cause disease. "In the off state, LvrB is fixed in a symmetrical and thus inactive form in which it cannot activate virulence factors," explains Elia Agustoni, first author of the study. "This off-position prevents the pathogen from producing virulence factors unnecessarily, i.e. when it is outside the body."
Active and "dangerous"
Signals from the host set a chain reaction in motion, as a result of which LvrB is chemically modified. This in turn leads to rearrangements of the protein structure. "LvrB changes its shape, the symmetry is broken, which virtually activates the protein," explains Agustoni. "In the 'on' state, LvrB transmits the signal to its partner protein, which the researchers were also able to identify. Together they activate virulence genes that enable Leptospira to multiply and spread in the body.
Significance for other infectious diseases
Agents that keep LvrB or related proteins in the inactive form are presumably a promising approach to attenuate the virulence of pathogens and prevent infections. This could also reduce the risk of antibiotic resistance.
The findings on the activation of LvrB go far beyond the understanding of leptospirosis. This mechanism affects a large number of similar signaling systems in bacteria, including numerous pathogens that infect humans, animals and plants. "Based on our results, many previously unknown cellular processes can now be researched," emphasizes Hiller. "They will also be used to develop new antibiotics and agrochemicals, such as pesticides."
Note: This article has been translated using a computer system without human intervention. LUMITOS offers these automatic translations to present a wider range of current news. Since this article has been translated with automatic translation, it is possible that it contains errors in vocabulary, syntax or grammar. The original article in German can be found here.
Original publication
Elia Agustoni, Ariel Mechaly, Joaquín Dalla Rizza, David Beriashvili, Kristyna Pluhackova, Polina Isaikina, Felipe Trajtenberg, Thomas Müntener, Elsio A. Wunder, Albert I. Ko, Tilman Schirmer, Alejandro Buschiazzo, Sebastian Hiller; "Activation mechanism of the full-length histidine kinase LvrB from pathogenic Leptospira"; Nature Communications, 2026-4-16
Other news from the department science
