Antibiotic-resistant bacteria find new strategies to avoid being killed by antibiotics. One of these strains that are resistant to most antibiotics is Pseudomonas aeruginosa, which is naturally found in soil and water, as well as in hospitals, nursing homes, and similar institutions for persons with weakened immune systems. Now, a team of researchers from the department of biochemistry and molecular biology and department of clinical microbiology at the University of Southern Denmark, has discovered a weakness in P. aeruginosa with the potential to become the target for a new way to attack it.

The findings are published in Microbiology Spectrum in the article titled, “The uncharacterized PA3040-3042 operon is part of the cell envelope stress response and a tobramycin determinant in a clinical isolate of Pseudomonas aeruginosa.”

The team discovered a mechanism, that reduces the formation of biofilm on the surface of P. aeruginosa. The formation of a sticky, slimy biofilm is a powerful tool used by bacteria to protect themselves against antibiotics—a trick also used by P. aeruginosa.

“This biofilm can be so thick and gooey that an antibiotic cannot penetrate the cell surface and reach its target inside the cell,” explained Clare Kirkpatrick, head of research at department of biochemistry and molecular biology, adding: “Maybe one day, we could pharmacologically stimulate this mechanism to reduce biofilm development on the surface of P. aeruginosa.”

Specifically, the researchers worked with three newly discovered genes in a lab-grown strain of P. aeruginosa. When they overexpressed these genes, they saw a strong reduction of biofilm. They also observed the system affected by the genes is part of the P. aeruginosa core genome.

“Being part of P. aeruginosa’s core genome, this system has been found in all investigated strains of P. aeruginosa, including a large variety of strains isolated from patients. So, there is reason to believe that reduction of biofilm via this system should be effective in all known strains of P. aeruginosa,” said Kirkpatrick.

It is not uncommon for patients infected with a P. aeruginosa strain to initially respond well to antibiotic treatment but then become resistant as the strain evolves resistance during treatment. Strains mutate, but their common core genome does not change.

The researchers activated the biofilm-reducing system by overexpressing genes. But they also discovered that the system is naturally stimulated by cell wall stress.

“So, if we stress the cell wall, it may naturally lead to a reduction in biofilm, making it easier for an antibiotic to penetrate the cell wall,” said Kirkpatrick, adding: “Currently, cell wall-targeted drugs are not widely used against P. aeruginosa, but perhaps, they could start to be used as additives to help reduce biofilm production and improve access of the existing antibiotics to the cells.”

The new findings could lead to novel strategies for not only P. aeruginosa, and may also help against other antibiotic-resistant bacteria.

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