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From Proteopedia
Pseudomonas aeruginosa Virulence Factor Regulator with cAMP ligand and Cl(triethylphosphine)gold(I)
Structural highlights
FunctionVFR_PSEAE Can bind cyclic AMP. Is a global regulator of virulence factor expression and is required for exotoxin A and protease production. Publication Abstract from PubMedPseudomonas aeruginosa is a leading cause of hospital-acquired infections. Treatment of P. aeruginosa infections is difficult given its multiple virulence mechanisms, intrinsic antibiotic resistance mechanisms, and biofilm-forming ability. Auranofin, an approved oral gold compound for rheumatoid arthritis treatment, was recently reported to inhibit the growth of multiple bacterial species. Here, we identify P. aeruginosa's global virulence factor regulator Vfr as one target of auranofin. We report the mechanistic insights into the inhibitory mechanism of auranofin and gold(I) analogues to Vfr through structural, biophysical, and phenotypic inhibition studies. This work suggests that auranofin and gold(I) analogues have potential to be developed as anti-virulence drugs against P. aeruginosa. Structural basis for the inhibitory mechanism of auranofin and gold(I) analogues against Pseudomonas aeruginosa global virulence factor regulator Vfr.,Zhang Y, Chew BLA, Wang J, Yuan M, Yam JKH, Luo D, Yang L Comput Struct Biotechnol J. 2023 Mar 13;21:2137-2146. doi: , 10.1016/j.csbj.2023.03.013. eCollection 2023. PMID:37007650[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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