Part of the research team in Bochum: Dr. Stephan Pienkoß, Dr. Sina Schäkermann, Dr. Soheila Javadi, and Professor Franz Narberhaus (from left)
Microbial Biology
New Virulence Regulator of Diarrhea Pathogen Discovered
Pathogenic bacteria often delay the activation of their virulence program until they are inside the host. Researchers have identified a new mechanism that controls this process.
Some pathogens use temperature as a trigger and activate virulence only after entering the warmer environment of a host. A research team from Ruhr University Bochum, Germany, and the University of Münster, Germany, investigated how a diarrheal pathogen suppresses its virulence outside of the human body. Their study focused on the DNA-binding protein Fis, which is more abundant at cooler ambient temperatures of around 25°C. Under these conditions, Fis represses the expression of virulence genes. When Fis is absent, a cascade of virulence genes is induced, and bacteria that are normally harmless at this temperature become lethal to poikilothermic moth larvae. The findings were published online in PLoS Pathogens on March 25, 2026.
The model organism used in this study, Yersinia pseudotuberculosis – a close relative of the notorious plague pathogen – is a true master of temperature perception. It uses ambient temperature as a signal to distinguish between a cool external environment and the warm conditions inside a host. While it was already known that RNA molecules enable direct temperature sensing, the current study reveals that the Fis protein also plays a regulatory role at the DNA level. “Fis functions as a molecular monitor that represses virulence genes at 25°C outside the host,” says Professor Franz Narberhaus from the Department of Microbial Biology at Ruhr University Bochum.
Fis represses virulence genes
Two things happen after entering the warm-blooded host: The production of proteins required for bacterial motility is prevented to evade detection by the human immune system, while virulence factors that weaken host defenses are induced. “In experiments with a Yersinia strain lacking the Fis protein, we observed an unexpected phenotype at 25°C,” reports Narberhaus. “The bacteria were completely immobile and secreted effector proteins that typically exert their harmful effects only in the gut.” These findings indicate that the absence of Fis disrupts the temperature-dependent balance between non-virulent and virulent states in the bacteria.
Infection of moth larvae confirms the function
These results raise the question of whether bacteria lacking the Fis protein are already infectious at 25°C. Bacterial virulence is typically examined in mice, which, like humans, are warm-blooded. However, such a model is not suitable for infection experiments at different temperatures. Instead, poikilothermic moth larvae proved to be a viable alternative. The Yersinia strain lacking Fis exhibited increased virulence at 25°C. Unlike the wild-type strain, it was able to kill the larvae at this low temperature. This finding indicates that the Fis protein represses virulence outside of the host.
The researchers in Bochum are now working to identify the precise molecular mechanisms by Fis exerts this regulatory control.