Antibiotic-resistant bacteria are a significant and growing threat to global health. One such bacterium is Pseudomonas aeruginosa which is naturally found in soil and water. However, it can also be found in hospitals, nursing homes, and similar institutions where individuals have weakened immune systems. Many of the P. aeruginosa strains found in hospitals are resistant to most antibiotics, meaning scientists must continually seek new methods to combat them.

A team of researchers from the Department of Biochemistry and Molecular Biology and the Department of Clinical Microbiology at the University of Southern Denmark has discovered a vulnerability in P. aeruginosa that could potentially be targeted for new treatments. 

The team, which published findings in Microbiology Spectrum, identified a mechanism that reduces the formation of biofilm on P. aeruginosa's surface and published. Biofilm, a sticky and slimy substance, is a powerful defense used by bacteria to protect themselves against antibiotics.

"This biofilm can be so thick and gooey that antibiotic cannot penetrate the cell surface and reach its target inside the cell," said Clare Kirkpatrick, head of research at the Department of Biochemistry and Molecular Biology. She added, "Maybe one day, we could pharmacologically stimulate this mechanism to reduce biofilm development on the surface of P. aeruginosa."

The researchers focused on three newly discovered genes in a lab-grown strain of P. aeruginosa. When overexpressed, these genes led to a significant reduction in biofilm. Importantly, the system affected by these genes is part of the P. aeruginosa core genome, found universally in all sequenced strains of this bacterium.

"Being part of [this bacterium’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," explained Clare Kirkpatrick.

Bacterial strains can evolve and mutate quickly under pressure. It is common for patients who initially responded well to antibiotics to develop resistance as the bacteria evolve. While strains mutate, their core genome remains unchanged. Which is why the team’s additional discovery could be so significant. 

In the course of their biofilm research, the team also found that this 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 antibiotics to penetrate the cell wall," said Clare Kirkpatrick. She added, "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."

When targeting infectious bacteria, there are limited attack points. Targets shared by both bacterial and human cells cannot be attacked without harming human cells as well. Bacterial and human cells share some targets, such as DNA replication and basic metabolic processes. However, the bacterial cell wall, which differs significantly from the human cell wall, remains a viable target.

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