Raloxifene attenuates Pseudomonas aeruginosa pyocyanin production and virulence.

摘要: Abstract There has been growing interest in disrupting bacterial virulence mechanisms as a form of infectious disease control through the use ‘anti-infective' drugs. Pseudomonas aeruginosa is an opportunistic pathogen noted for its intrinsic antibiotic resistance that causes serious infections requiring new therapeutic options. In this study, analysis P. PAO1 deduced proteome was performed to identify pathogen-associated proteins. A computational screening approach then used discover drug repurposing opportunities, i.e. identifying approved drugs bind and potentially disrupt protein targets. The selective oestrogen receptor modulator raloxifene, currently prevention osteoporosis and/or invasive breast cancer post-menopausal women, predicted from screen PhzB2. PhzB2 involved production blue pigment pyocyanin produced via phenazine biosynthesis pathway. Pyocyanin toxic eukaryotic cells shown play role infection mouse model, making it attractive target anti-infective discovery. Raloxifene found strongly attenuate Caenorhabditis elegans model infection. Treatment wild-type strains PA14 with raloxifene resulted dose-dependent reduction vitro; were also reduced phzB2 insertion mutant. These results suggest may be suitable further development such already computationally screened repurposed novel anti-infective/anti-virulence agents.