PLoS ONE: a new weapon against antibiotic-resistant bacteria

The irrational use of antibiotics has prompted bacteria to become resistant to this treatment
.
This phenomenon, known as antibiotic resistance, is now recognized by the World Health Organization as one of
the greatest threats to health.
The lack of treatment for multidrug-resistant bacteria could take us back to a time when
millions of people died from pneumonia or salmonella.
The bacterium Klebsiella pneumoniae is very common in hospitals, particularly virulent and one of
the pathogens that our weapons are becoming dull.
A team of researchers at the University of Geneva (UNIGE) found that the anti-herpes molecule edoxudine, discovered in the 60s, weakened the skin's protective surface, Klebsiella, making them easier to clear
by immune cells.
These results can be read in the journal PLoS Library? Synthesis".

Klebsiella pneumoniae can cause respiratory, intestinal, and urinary tract infections
.
Because they are resistant to most common antibiotics and are highly toxic, some strains can kill
between 40% and 50% of infected people.
There is an urgent need to develop new therapeutic molecules to combat it
.
"Medicine has relied on antibiotics to remove pathogenic bacteria since the 2030s," explains Pierre Cosson, a professor in the Department of Cell Physiology and Metabolism at the United Nations University School of Medicine, who led the study
.
"But there are other viable approaches, which include trying to weaken the bacteria's defense system so that they can no longer escape the immune system
.
" This approach seems more promising because Klebsiella pneumoniae's virulence stems in large part from its ability to
evade attacks from infected cells.
”

An amoeba as a model

To determine whether the bacteria were weakened, UNIGE scientists used an experimental model with striking characteristics: the dikiamoeba amoeba
.
This single-celled organism feeds on bacteria and uses the same mechanism
that immune cells kill pathogens by trapping and ingesting them.
"We genetically modified the amoeba so that it could tell us if the bacteria it encountered were poisonous
.
This very simple system then allowed us to test thousands of molecules and identify those that reduce bacterial toxicity," explains
Pierre Cosson.

Weaken bacteria without killing them

Developing a drug is a long and expensive process that does not guarantee results
.
So scientists at the United Nations Institute for AIDS Research opted for a faster and safer strategy: reviewing existing drugs to identify possible new therapeutic indications
.
The research team evaluated the efficacy of hundreds of drugs already on the market against Klebsiella pneumoniae with a wide range of therapeutic indications
.
A drug for the treatment of herpes, edodine, proved to be particularly promising
.

"By altering the surface layer that protects bacteria from the external environment, this pharmacological product makes bacteria vulnerable
.
Unlike antibiotics, edodine does not kill bacteria, which limits the risk of developing resistance, which is a major advantage of this antiviral strategy," the researcher said
.

While the effectiveness of this treatment in humans has yet to be proven, the results of this study are encouraging: Edodine works against even the deadliest strain of Klebsiella pneumoniae, and at lower concentrations than prescribed for herpes treatment
.
Pierre Coussen concludes: "Sufficiently weakening bacteria without killing them is a delicate strategy, but in the short and long term, it could be a
winner.
"