Increasingly, bacteria are becoming resistant to antibiotics. When no antibiotic is effective, even "simple" infections can lead to patient death. Researchers have found a new approach for eliminating the bacterium Pseudomonas aeruginosa.
The tenacious pathogen Pseudomonas aeruginosa Pseudomonas aeruginosa frequently survives antibiotic therapies1. Its complex communication mechanisms are resistant to attacks by the body’s natural immune system. In particular, its adaptability and ability to coordinate signalling substances make it difficult for researchers to fight the resistant hospital germ.
The bacterium eludes antibiotic agents by encapsulating itself through a biofilm that is difficult to penetrate, or it uses small pumps to push the drug’s toxins out of the biofilm, so that these substances cannot reach the bacterium’s metabolism. The bacteria coordinate their strategies with each other. They release signal molecules that help them to trigger corresponding counter-reactions should a certain threshold value (“quorum”) be reached. This special communication method is called “quorum sensing”. Pseudomonas aeruginosa has three such communication methods.
Researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken (both in Germany) have now discovered that one of these communication systems (the so-called pqs system, or “pseudomonas quinolone signal”) is possibly a weak point of the pathogen, and could offer a way to attack persistent bacterium2.
Researchers have known for a long time that Pseudomonas aeruginosa works with a large spectrum of signal molecules – but they did not know how the diversity of these molecules develops specifically. Scientist Florian Witzgall, PhD student with Professor Wulf Blankenfeldt (head of the Department Protein Structure and Form at the HZI), recently investigated this in more detail.
It seems the signal diversity of the bacterium results from the interaction of two proteins: one forms the stabilizer (PqsB), the other carries out the chemical reaction (PqsC). The protein complex (PqsBC) is extremely flexible. “PqsBC is the first example of this protein family in which mobility has actually been proven by different crystal structures,” explains Florian Witzgall in a statement from the Helmholtz Centre3.
Now the researchers’ aim is to develop new drugs that paralyse the mobility of PqsBC. This could inhibit the protein complex and interrupt the communication of Pseudomonas aeruginosa.
Pseudomonas aeruginosa, Robert-Koch-Institut
The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH‐like 2‐Heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) Biosynthesis Enzyme PqsBC, Witzgall F et al., ChemBioChem