A team of researchers finds how a drug used to treat herpes can fight bacterium resistant to antibiotics by weakening its defence mechanisms, according to a study published in the journal PLOS One.
The excessive use of antibiotics has led to the development of bacteria that are resistant to this type of treatment. The World Health Organisation (WHO) considers antibiotic resistance of the greatest threat to human health at the moment. This is not surprising, given how lack of treatment can take us back to a time when millions of people died of pneumonia or even salmonella.
The bacterium Klebsiella pneumoniae is very common in hospitals and one of the most resistant to antibiotics. Now, a team from the University of Geneva, Switzerland, found out how edoxudine — a drug commonly used to treat herpes — can weaken the protective surface of the Klebsiella bacteria, making it easier to eliminate and destroy.
This bacterium causes respiratory, urinary, and intestinal tract infections, with some of its strains being 40-50% fatal to infected patients. As a result, there is an urgent need to develop new drugs to treat these patients. “Since the 1930s, medicine has relied on antibiotics to get rid of pathogenic bacteria,” said 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.”
To find out how this bacterium is affected, the team used the amoeba as as experimental model. This single-cell organism eats bacteria using the same approach that immune cells use to kill pathogens. “We genetically modified this amoeba so that it could tell us whether the bacteria it encountered were virulent or not. This very simple system then enabled us to test thousands of molecules and identify those that reduced bacterial virulence,” explained Pierre Cosson.
Developing a new drug is an expensive and time-consuming process, and so the team from Geneva looked for a quicker and safer strategy: review already existing drugs and identified new potential uses. The researchers assessed how hundreds of drugs acted on Klebsiella pneumoniae and found that edoxudine seemed particularly promising. “By altering the surface layer that protects the bacteria from their external environment, this pharmacological product makes it vulnerable. Unlike an antibiotic, edoxudine does not kill the bacteria, which limits the risk of developing resistance, a major advantage of such an anti-virulence strategy,” said the researcher.
The effectiveness of this drug has not been tested yet, but the preliminary results are promising: edoxudine seems to act even on the most virulent strains and at lower concentrations than needed 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 terms,” concluded Pierre Cosson.