RESUMEN
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.
Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/metabolismo , Auranofina/farmacología , Auranofina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Factores de Virulencia/metabolismo , Factores de Virulencia/farmacología , Factores de Virulencia/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Biopelículas , Percepción de Quorum , Proteínas Bacterianas/farmacologíaRESUMEN
Aided by high level ab initio computational modeling, we successfully designed and experimentally proved a new set of backbone-rigidified pyridine-based folding oligoamides that require approximately four repeating units to form a helical turn.