Auranofin inhibits virulence pathways in Pseudomonas aeruginosa
Joey Kuok Hoong Yam1, Leon Zhen Wei Tan2, Ziyan Hong1
1Singapore Center for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore.
Abstract:
Pseudomonas aeruginosa is widely attributed as the leading cause of hospital-acquired infections. Due to intrinsic antibiotic resistance mechanisms and the ability to form biofilms, P. aeruginosa infections are challenging to treat. P. aeruginosa employs multiple virulence mechanisms to establish infections, many of which are controlled by the global virulence regulator Vfr. An attractive strategy to combat P. aeruginosa infections is thus the use of anti-virulence compounds. Here, we report the discovery that FDA-approved drug auranofin attenuates virulence pathways in P. aeruginosa, including quorum sensing (QS) and Type IV pili (TFP). We show that auranofin acts via multiple targets, one of which being Vfr. Consistent with inhibition of QS and TFP expression, we show that auranofin attenuates biofilm maturation, and when used in combination with colistin, displays strong synergy in eradicating P. aeruginosa biofilms. Auranofin may have immediate applications as an anti-virulence drug against P. aeruginosa infections.
Insights
The FDA-approved drug auranofin reduces virulence in Pseudomonas aeruginosa by targeting key pathways like quorum sensing and Type IV pili. This drug shows synergy with colistin, offering a promising anti-virulence strategy against difficult-to-treat infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pseudomonas aeruginosa is a primary cause of hospital-acquired infections.
- Its intrinsic antibiotic resistance and biofilm formation make infections difficult to treat.
- Virulence factors, regulated by Vfr, are crucial for P. aeruginosa pathogenesis.
Purpose of the Study:
- To identify anti-virulence compounds effective against P. aeruginosa.
- To investigate the potential of FDA-approved drugs as anti-virulence agents.
Main Methods:
- Screening of FDA-approved drugs for anti-virulence activity.
- Assessing the impact of auranofin on P. aeruginosa virulence pathways (quorum sensing, Type IV pili).
- Investigating auranofin's mechanism of action, including its effect on the Vfr regulator.
- Evaluating auranofin's effect on biofilm maturation and its synergy with colistin.
Main Results:
- Auranofin was identified as a potent attenuator of P. aeruginosa virulence pathways.
- Auranofin inhibits quorum sensing and Type IV pili expression, and targets Vfr.
- Auranofin reduces biofilm maturation and demonstrates significant synergy with colistin in biofilm eradication.
Conclusions:
- Auranofin exhibits significant anti-virulence properties against P. aeruginosa.
- Its ability to inhibit multiple virulence factors and potentiate antibiotics makes it a promising therapeutic candidate.
- Auranofin may offer a novel strategy for treating challenging P. aeruginosa infections.
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