article · Antibiotics
This research investigated the potential of allopurinol, an FDA-approved drug, to inhibit quorum sensing (QS) in *Pseudomonas aeruginosa*, a bacterium responsible for many healthcare-associated infections. The study found that allopurinol significantly reduced the production of QS-controlled virulence factors, such as violacein, in *P. aeruginosa* PAO1. In infected mice, allopurinol decreased bacterial infiltration and tissue congestion in the liver and kidneys. Computational analysis suggested allopurinol competes with natural signalling molecules for binding to key QS receptors. Molecular tests confirmed that allopurinol downregulated genes involved in QS. The findings suggest allopurinol is a promising QS inhibitor that could be useful in treating *P. aeruginosa* infections.
Antibiotic resistance is a major global health threat, making new treatment strategies crucial. This research explores a novel approach to combat bacterial infections by disarming bacteria's ability to cause harm rather than killing them, potentially reducing the development of resistance. It offers a new pathway for treating difficult-to-manage infections like those caused by *Pseudomonas aeruginosa*.
This research identifies an existing FDA-approved drug, allopurinol, as a potential quorum sensing inhibitor for *Pseudomonas aeruginosa* infections. This could lead to new therapeutic strategies for healthcare-associated infections, particularly those resistant to conventional antibiotics. The use of an already approved drug suggests a potentially faster pathway to clinical application, offering a new treatment option for clinicians and patients. This is early-stage research demonstrating a new application for an existing drug.
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<i>Pseudomonas aeruginosa</i> can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the <i>P. aeruginosa</i> PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled <i>Chromobacterium violaceum</i> CV026 violet pigment violacein and other <i>P. aeruginosa</i> QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of <i>P. aeruginosa</i> and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of <i>P. aeruginosa</i> infection.
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DOI: 10.3390/antibiotics10111385
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