University of Fribourg researchers discover that hydrogen cyanide, produced by dangerous bacteria, helps the bacteria evade the patients' immune defenses.

Researchers from the University of Fribourg have discovered that Pseudomonas aeruginosa, a major cause of hospital-acquired infections, uses hydrogen cyanide as a defense mechanism to weaken the body's innate immune response. The findings, published in The Journal of Infectious Diseases, open the door to innovative therapeutic approaches aimed at improving the treatment of difficult bacterial infections.

The study, led by a joined effort of Prof. Csaba Szabó and Prof. Patrice Nordmann from the Department of Oncology, Microbiology and Immunology, demonstrates that hydrogen cyanide produced by P. aeruginosa helps the bacterium survive attacks from immune cells. When researchers genetically disabled cyanide production, the bacteria became significantly more vulnerable to destruction by macrophages, one of the body's first lines of defense against infection.

The team further showed that compounds capable of neutralizing cyanide, including vitamin B12 derivatives, enhanced the ability of immune cells to eliminate the bacteria. In animal models, cyanide-deficient bacteria were cleared much more effectively, resulting in substantially lower bacterial burdens in infected tissues.

Boosting the body’s natural defences
«Our findings reveal that hydrogen cyanide is not merely a toxic by-product of bacterial metabolism, but a genuine virulence factor that helps bacteria resist immune attack,» explains Prof. Szabó «Targeting bacterial cyanide production or neutralizing cyanide may represent a completely new strategy to help the immune system fight infections.»

Pseudomonas aeruginosa is a particularly important pathogen because it frequently causes severe infections in hospitalized and immunocompromised patients and is well known for its ability to develop antibiotic resistance. The discovery is therefore especially relevant at a time when antimicrobial resistance is recognized as a growing global health threat.

Rather than directly killing bacteria, future therapies based on cyanide scavenging could strengthen the body's natural defenses and improve bacterial clearance. Such approaches could complement existing antibiotics and help address infections that are increasingly difficult to treat.

The research was conducted at the University of Fribourg in collaboration with the University of California San Diego and was supported by a University of Fribourg Pool Grant.

Publication: Szabó C., Sousa Santos S., Findlay J., Bremer O., Petrosino M., Philipp T.M., Kierońska-Rudek A., Zuhra K., Boss G.R., Nordmann P., «Hydrogen cyanide generation by Pseudomonas aeruginosa blunts the host innate immune response», The Journal of Infectious Diseases