Drug-resistant bacteria continuously evolve new tactics to evade the effects of antibiotics.
Bacteria, such as Pseudomonas aeruginosa, are adept at developing resistance to antibiotics. This bacterium is commonly found in environments like soil and water as well as in healthcare facilities housing individuals with weakened immune systems. Many strains of P. aeruginosa in healthcare settings have evolved resistance to a wide range of antibiotics, necessitating ongoing efforts in scientific research to find new ways of combating them.
A team of researchers from the University of Southern Denmark, specifically the Departments of Biochemistry and Molecular Biology and Clinical Microbiology, have made a breakthrough in identifying a vulnerability in P. aeruginosa that could serve as a target for a novel treatment approach. Their study results have been published in the journal Microbiology Spectrum, authored by Clare Kirkpatrick, Magnus Z. Østergaard, Flemming D. Nielsen, and Mette H. Meinfeldt.
Discovery of Biofilm Weakness
The researchers unearthed a mechanism that reduces the formation of biofilm on the surface of P. aeruginosa. Biofilm, a sticky and slimy layer, is employed by bacteria as a defense mechanism against antibiotics. This protective biofilm can be so dense that antibiotics are unable to penetrate the bacterial cell surface and reach their target within the cell.
Clare Kirkpatrick, the head of research at the Department of Biochemistry and Molecular Biology, explained, “This biofilm can be so thick and gooey that antibiotic cannot penetrate the cell surface and reach its target inside the cell. Maybe one day, we could pharmacologically stimulate this mechanism to reduce biofilm development on the surface of P. aeruginosa.”
Identification of Three Novel Genes
The researchers focused on three recently discovered genes within a laboratory-grown strain of P. aeruginosa. When these genes were overexpressed, a significant reduction in biofilm formation was observed. Importantly, these genes are part of the core genome of P. aeruginosa, indicating their presence across various strains of the bacterium sequenced to date.
Clare Kirkpatrick highlighted, “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.”
Stress-Induced Cell Wall Response
In their experiments, the researchers induced the biofilm reduction system by overexpressing these genes. They also noted that the system naturally responds to cell wall stress.
Clare Kirkpatrick elaborated, “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. Currently, cell wall-targeted drugs are not widely used against P. aeruginosa, but perhaps they could be utilized as supplements to diminish biofilm production and enhance antibiotic access to the cells.”
Distinguishing Bacterial Cell Walls
In combating bacterial infections, there are limited targets available for intervention. Targets shared between bacterial and human cells cannot be targeted by antibiotics without affecting human cells.
Common targets between bacterial and human cells include DNA replication processes, basic glucose metabolism, and cell respiration mechanisms. Bacteria possess unique targets such as certain protein functions and the bacterial cell wall, presenting an attractive target due to its distinctiveness from human cell walls.
