Abstract
Quorum sensing regulates virulence factors in Pseudomonas aeruginosa and coordinate bacterial pathogenicity. Therefore, the quorum sensing system in Pseudomonas aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the effects of sub-minimum inhibitory concentrations of (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene) propane hydrazide (lacto hydrazone) against Pseudomonas aeruginosa quorum sensing related virulence factors. The minimum inhibitory concentration of lacto hydrazone was determined against Pseudomonas aeruginosa PAO1 using broth microdilution method and the effect of subinhibitory concentrations of this compound on virulence factors was also determined. Treated PAO1 cultures in the presence of lacto hydrazone at subinhibitory concentrations showed significant inhibition of virulence factors including motility, biofilm formation, alginate and pyocyanin production, and susceptibility to H2O2 (P < 0.001). Because of quorum sensing is a promising target for anti-virulence therapy and LasR is an important regulatory protein of Pseudomonas aeruginosa quorum sensing system, we carried out molecular docking for understanding the interactions of lacto hydrazone with the LasR receptor. The results of the best docked conformer showed the binding energy of −7.31 kcal/mol and displayed interactions as the natural autoinducer with hydrogen bonds involving Arg 61, Trp 60, Asp 73, and Ser 129 in the active site of LasR. The results indicate that subinhibitory concentrations of lacto hydrazone exhibited inhibitory effects on Pseudomonas aeruginosa quorum sensing related virulence factors.
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The authors are grateful to the University of Zanjan and Zanjan University of Medical Sciences for financial support of this study.
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Heidari, A., Haghi, F., Noshiranzadeh, N. et al. (S,E)-2-hydroxy-N-(2-hydroxy-5-nitrobenzylidene) propane hydrazide as a quorum sensing inhibitor of Pseudomonas aeruginosa . Med Chem Res 26, 1947–1955 (2017). https://doi.org/10.1007/s00044-017-1908-8
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DOI: https://doi.org/10.1007/s00044-017-1908-8