Bacteria are germs that can be found both inside and outside of our bodies. Most germs are harmless, and some can even be beneficial to humans, but some bacteria can cause infections such as strep throat and urinary tract infections. Antibiotics are critical tools for preventing and treating infections caused by specific bacteria in humans, animals, and crops. Antibiotics are one of our most powerful drugs in the fight against life-threatening bacterial infections.
The overuse of antibiotics has pushed bacteria to develop resistance mechanisms to this type of treatment. The WHO now considers antibiotic resistance to be one of the most serious threats to human health. The lack of treatment against multi-resistant bacteria could bring us back to a time when millions of people died of pneumonia or salmonella.
The overuse of antibiotics has pushed bacteria to develop resistance mechanisms to this type of treatment. The WHO now considers antibiotic resistance to be one of the most serious threats to human health. The lack of treatment for multi-resistant bacteria could return us to a time when millions of people died from pneumonia or salmonella.
Klebsiella pneumoniae, a pathogen that is common in hospitals and particularly virulent, is one of the pathogens against which our weapons are becoming blunt. A team from the University of Geneva (UNIGE) discovered that edoxudine, an anti-herpes molecule discovered in the 1960s, weakens the protective surface of Klebsiella bacteria, making them easier to eliminate for immune cells. These results can be read in the journal PLOS One.
Klebsiella pneumoniae causes many respiratory, intestinal and urinary tract infections. Due to its resistance to most common antibiotics and its high virulence, some of its strains can be fatal for 40% to 50% of infected people. There is an urgent need to develop new therapeutic molecules to counter it.
This pharmacological product makes bacteria vulnerable by altering the surface layer that protects them from their surroundings. Unlike antibiotics, edoxudine does not kill bacteria, limiting the risk of resistance development, which is a significant advantage of such an anti-virulence strategy.
Pierre Cosson
“Since the 1930s, medicine has relied on antibiotics to get rid of pathogenic bacteria,” explains Pierre Cosson, professor in the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine, who led this research. “But other approaches are possible, among which trying to weaken the bacteria’s defence system so that they can no longer escape the immune system. This avenue seems all the more promising as the virulence of Klebsiella pneumoniae stems largely from its ability to evade attacks from immune cells.”
An amoeba as a model
The UNIGE scientists used an unusual experimental model to determine whether or not the bacteria were weakened: the amoeba Dictyostelium. This single-cell organism feeds on bacteria by capturing and ingesting them, similar to how immune cells kill pathogens. “This amoeba was genetically modified so that it could tell us whether the bacteria it encountered were virulent or not. We were then able to test thousands of molecules and identify those that reduced bacterial virulence using this very simple system” Pierre Cosson explains.
Weakening the bacteria without killing them
Developing a drug is a long and expensive process, with no guarantee of results. The UNIGE scientists therefore opted for a quicker and safer strategy: reviewing existing drugs to identify possible new therapeutic indications. The research team evaluated the effect on Klebsiella pneumoniae of hundreds of drugs already on the market, with a wide range of therapeutic indications. A drug developed to combat herpes, edoxudine, proved particularly promising.
“This pharmacological product makes bacteria vulnerable by altering the surface layer that protects them from their surroundings. Unlike antibiotics, edoxudine does not kill bacteria, limiting the risk of resistance development, which is a significant advantage of such an anti-virulence strategy” says the researcher
Although the efficacy of such a treatment in humans has yet to be confirmed, the findings of this study are encouraging: edoxudine acts on even the most virulent strains of Klebsiella pneumoniae, and at lower concentrations than those used to treat herpes. “Sufficiently weakening the bacteria without killing them is a subtle strategy, but one that could prove to be a winner in the short and long term,” Pierre Cosson concludes.
