Random evolution turns an environmental bacterium into a dangerous pathogen
New findings on the virulence mechanism of Chromobacterium haemolyticum
| by Friederike Gawlik
Researchers from the Leibniz-HKI in Jena together with colleagues from the University of Melbourne have elucidated a central virulence mechanism of the opportunistic environmental bacterium Chromobacterium haemolyticum. The study, published in the journal mBio, shows how certain natural products of the bacterium both promote its environmental adaptation and favor severe infections in humans and animals.
“We looked at a bacterium that lives in the environment and is normally completely harmless,” says Ingrid Richter, who led the study together with department head Christian Hertweck at the Leibniz-HKI. “However, if it comes into contact with humans or animals, it can become a pathogen. The species name haemolyticum already suggests that it breaks down blood – but what exactly causes this effect was previously unknown.” C. haemolyticum was first described in 2008 and has since been detected in various environmental samples, particularly in the waters of tropical and subtropical regions, but also in clinical samples of sometimes life-threatening infections.
As the researchers have now discovered, a family of cyclic lipodepsipeptides is responsible for the strong haemolytic activity of C. haemolyticum. These natural substances include the antifungal jagaricin as well as two newly described congeners, jagaricin B and C. These compounds destroy red blood cells and thus contribute significantly to the pathogenicity of the bacterium – and they can cause immense damage to the host’s body. Through targeted gene deletions, the scientists were able to show that bacteria without the corresponding gene cluster no longer trigger haemolysis.
“We had previously investigated another strain that produces jagaricin. A substance that was discovered at the Leibniz-HKI and also has a hemolytic effect,” explains Richter. “We then used genome mining, i.e. the targeted search in the genome for blueprints for certain substances, and found a gene cluster that is contained in many representatives of the Chromobacterium group. But we didn’t do this alone. The team from Melbourne supported us very well with the sequencing of the genomes and the bioinformatic analyses. It was particularly exciting for us to discover that two environmental strains from completely different sources produce the same molecule. This indicates that it may fulfill an important ecological function.”
And indeed: in addition to damaging blood cells, jagaricins play an important role in the environmental fitness of the bacterium. They are significantly involved in biofilm formation and swarm movement. Both are processes that enable C. haemolyticum to open up new habitats and prevail against competing microbes. “On the agar plate you can see very clearly how the wild type swarms out and in liquid cultures you can see how it forms biofilms. The mutant can no longer do this without the gene cluster,” says Richter.
This dual function makes the substances so-called “dual-use” virulence factors: on the one hand, they promote the survival of the bacterium in the environment, which appears to be their primary function. On the other hand, they act as virulence factors in humans and make them ill. The study thus provides an example of so-called “accidental” evolution: in this case, disease-promoting mechanisms can arise from characteristics that actually serve to adapt to the environment. This phenomenon is also observed in other opportunistic pathogens.
“Such findings help us to better assess the risk potential of environmental microbes,” says Richter. “In the long term, they also open up new avenues for anti-virulence strategies that specifically block such mechanisms.”
The study was carried out as part of the “Balance of the Microverse” Cluster of Excellence and the ChemBioSys Collaborative Research Center at Friedrich Schiller University Jena.
Original publication
Dumjahn L, Wein P, Molloy EM, Scherlach K, Trottmann F, Meisinger PR, Judd LM, Pidot SJ, Stinear TP, Richter I, Hertweck C (2025) Dual-use virulence factors of the opportunistic pathogen Chromobacterium haemolyticum mediate hemolysis and colonization. mBio e0360524, https://doi.org/10.1128/mbio.03605-24.
