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The 9H-fluoren vinyl ether derivative SAM461 inhibits bacterial luciferase activity and protects Artemia franciscana from luminescent vibriosis

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Abstract
Vibrio campbellii is a major pathogen in aquaculture. It is a causative agent of the so-called "luminescent vibriosis," a life-threatening condition caused by bioluminescent Vibrio spp. that often involves mass mortality of farmed shrimps. The emergence of multidrug resistant Vibrio strains raises a concern and poses a challenge for the treatment of this infection in the coming years. Inhibition of bacterial cell-to-cell communication or quorum sensing (QS) has been proposed as an alternative to antibiotic therapies. Aiming to identify novel QS disruptors, the 9H-fluroen-9yl vinyl ether derivative SAM461 was found to thwart V. campbellii bioluminescence, a QS-regulated phenotype. Phenotypic and gene expression analyses revealed, however, that the mode of action of SAM461 was unrelated to QS inhibition. Further evaluation with purified Vibrio fischeri and NanoLuc luciferases revealed enzymatic inhibition at micromolar concentrations. In silico analysis by molecular docking suggested binding of SAM461 in the active site cavities of both luciferase enzymes. Subsequent in vivo testing of SAM461 with gnotobiotic Artemia franciscana nauplii demonstrated naupliar protection against V campbellii infection at low micromolar concentrations. Taken together, these findings suggest that suppression of luciferase activity could constitute a novel paradigm in the development of alternative anti-infective chemotherapies against luminescent vibriosis, and pave the ground for the chemical synthesis and biological characterization of derivatives with promising antimicrobial prospects.
Keywords
NONLUMINESCENT ISOGENIC VIBRIOS, DRUG DISCOVERY, HARVEYI, VIRULENCE, SYSTEM, IDENTIFICATION, COLONIZATION, AQUACULTURE, REGULATOR, PATHOGEN, vinyl ether, luciferase, Artemia, vibriosis, alternative anti-infectives

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Chicago
Martin-Rodriguez, Alberto J, Sergio J Alvarez-Mendez, Caroline Overa, Sri Kartik Baruah, Tânia Lourenço De Abreu, Parisa Norouzitallab, Peter Bossier, Victor S Martin, and Jose J Fernandez. 2018. “The 9H-fluoren Vinyl Ether Derivative SAM461 Inhibits Bacterial Luciferase Activity and Protects Artemia Franciscana from Luminescent Vibriosis.” Frontiers in Cellular and Infection Microbiology 8.
APA
Martin-Rodriguez, A. J., Alvarez-Mendez, S. J., Overa, C., Baruah, S. K., Lourenço De Abreu, T., Norouzitallab, P., Bossier, P., et al. (2018). The 9H-fluoren vinyl ether derivative SAM461 inhibits bacterial luciferase activity and protects Artemia franciscana from luminescent vibriosis. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 8.
Vancouver
1.
Martin-Rodriguez AJ, Alvarez-Mendez SJ, Overa C, Baruah SK, Lourenço De Abreu T, Norouzitallab P, et al. The 9H-fluoren vinyl ether derivative SAM461 inhibits bacterial luciferase activity and protects Artemia franciscana from luminescent vibriosis. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY. 2018;8.
MLA
Martin-Rodriguez, Alberto J et al. “The 9H-fluoren Vinyl Ether Derivative SAM461 Inhibits Bacterial Luciferase Activity and Protects Artemia Franciscana from Luminescent Vibriosis.” FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY 8 (2018): n. pag. Print.
@article{8591152,
  abstract     = {Vibrio campbellii is a major pathogen in aquaculture. It is a causative agent of the so-called "luminescent vibriosis," a life-threatening condition caused by bioluminescent Vibrio spp. that often involves mass mortality of farmed shrimps. The emergence of multidrug resistant Vibrio strains raises a concern and poses a challenge for the treatment of this infection in the coming years. Inhibition of bacterial cell-to-cell communication or quorum sensing (QS) has been proposed as an alternative to antibiotic therapies. Aiming to identify novel QS disruptors, the 9H-fluroen-9yl vinyl ether derivative SAM461 was found to thwart V. campbellii bioluminescence, a QS-regulated phenotype. Phenotypic and gene expression analyses revealed, however, that the mode of action of SAM461 was unrelated to QS inhibition. Further evaluation with purified Vibrio fischeri and NanoLuc luciferases revealed enzymatic inhibition at micromolar concentrations. In silico analysis by molecular docking suggested binding of SAM461 in the active site cavities of both luciferase enzymes. Subsequent in vivo testing of SAM461 with gnotobiotic Artemia franciscana nauplii demonstrated naupliar protection against V campbellii infection at low micromolar concentrations. Taken together, these findings suggest that suppression of luciferase activity could constitute a novel paradigm in the development of alternative anti-infective chemotherapies against luminescent vibriosis, and pave the ground for the chemical synthesis and biological characterization of derivatives with promising antimicrobial prospects.},
  articleno    = {368},
  author       = {Martin-Rodriguez, Alberto J and Alvarez-Mendez, Sergio J and Overa, Caroline and Baruah, Sri Kartik and Lourenço De Abreu, Tânia and Norouzitallab, Parisa and Bossier, Peter and Martin, Victor S and Fernandez, Jose J},
  issn         = {2235-2988},
  journal      = {FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY},
  keywords     = {NONLUMINESCENT ISOGENIC VIBRIOS,DRUG DISCOVERY,HARVEYI,VIRULENCE,SYSTEM,IDENTIFICATION,COLONIZATION,AQUACULTURE,REGULATOR,PATHOGEN,vinyl ether,luciferase,Artemia,vibriosis,alternative anti-infectives},
  language     = {eng},
  pages        = {11},
  title        = {The 9H-fluoren vinyl ether derivative SAM461 inhibits bacterial luciferase activity and protects Artemia franciscana from luminescent vibriosis},
  url          = {http://dx.doi.org/10.3389/fcimb.2018.00368},
  volume       = {8},
  year         = {2018},
}

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