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16 July 2024Infectious microorganisms use a dense, sticky biofilm to protect themselves from medications. Danish researchers have now found a way to end this strategy.
The antibiotic resistant bacteria They are experts in developing new strategies to avoid being eliminated by antibiotics, which has generated one of the most worrying global health problems. The World Health Organization (WHO) estimates that about 11 million people die from bacterial sepsis each year.
One of these microorganisms is Pseudomonas aeruginosa, which is found naturally in soil and water, but also in hospitals, nursing homes or primary care centers, where there may be people with weakened immune systems.
Researchers from the University of Southern Denmark, led by the microbiologist Clare Kirkpatrick, have now discovered a mechanism that reduces the formation of a dense layer on the surface of bacteria. It is a powerful tactic, like a shield, that these microorganisms develop to avoid being attacked by antibiotics and that also uses P. aeruginosa. The results of the work have been published in the journal Microbiology Spectrum.
«This biofilm that the bacteria forms is so thick and sticky that the antibiotic cannot penetrate or reach its target inside the cell»
Clare Kirkpatrick, Study Leader (University of Southern Denmark)
Kirkpatric explains to SINC how the bacteria forms this protective layer: “It detects that it is in contact with a suitable surface, or that there is a high bacterial density in the environment, and it begins to manufacture a large amount of polysaccharide material of biofilm and to transport it out of the cell.”
Then, “it produces a thick layer outside the cells, which mixes and firmly adheres the bacteria to each other and to the surface. The density of the material slows down the diffusion of antibiotics, so they only come into contact with cells gradually and often these drugs do not reach a concentration sufficient to kill them.”
In other words, “this biofilm is so thick and sticky that the antibiotic cannot penetrate or reach its target inside the cell,” he emphasizes.
three genes
To see how this material that protects the bacteria could be destroyed, Danish researchers worked with three newly discovered genes (named PA1371-1372, PA2732 and PA2735) in a strain of P. aeruginosa grown in a laboratory.

When they increased the expression of these genes, they observed a strong reduction in biofilm. The important thing is that the system affected by the genes is part of the core genome of P. Aeruginosa. This means that it is universally found in all strains of this bacterial species sequenced so far, the authors say.
Kirkpatrick explains that “by forming part of the core genome of the bacteria, this mechanism has been found in all investigated variants of the microorganism, including a wide variety of strains isolated from patients. Therefore, there is reason to believe that biofilm reduction by this method could be effective in all known strains of P. aeruginosa«.
«We believe that reducing the biofilm of bacteria, by overexpression of these genes, could be effective in all known strains of 'P. Aeruginosa'»
Clare Kirkpatrick
Bacteria can evolve individually and mutate rapidly and constantly when under pressure. It is not uncommon for patients infected with a variant of P. aeruginosa initially respond well to antibiotic treatment, but then become resistant as microorganisms develop resistance during treatment. Strains mutate, but their common core genome does not change.
Stress the cell membrane
In their experiments, the researchers activated the biofilm reducing system by overexpressing genes. But they also discovered that the mechanism is stimulated naturally by the cell wall stress.
“We have also discovered that cell membrane tension induces activation of gene expression, and that this naturally reduces the bacteria's protective layer, although we still don't know exactly how,” says Kirkpatrick.
In the future, “we would like to look for pharmacological methods to induce gene activation even more effectively, or perhaps increase the activity of the gene products, to try to achieve the same effect.
«Drugs targeting cell membranes are not widely used against 'P. Aeruginosa'. "Perhaps they could be used as additives to reduce biofilm production and improve the accessibility of antibiotics."
Clare Kirkpatrick
According to the microbiologist, at the moment, “drugs directed at cell membranes are not routinely used against P. aeruginosa, "But perhaps they could begin to be used as additives to reduce biofilm production and improve the access of antibiotics to cells."
Perhaps, he concludes, “these additives could be included as 'auxiliary antibiotics'. For example, incorporated into medical devices or bandages, and thus be useful for their antibiofilm properties against infections by P. aeruginosa. “In this way, ‘reference’ antibiotics could be helped to do their job better for the benefit of patients.”
Source: Travel SINC
Reference: Magnus Z.Østergaard, Clare Kirkpatrick: “The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin resistance determinant in a clinical isolate of Pseudomonas aeruginosa. Microbiology Spectrum (2024)