Abstract

The cell density-dependent mechanism, quorum sensing (QS), regulates the expression of virulence factors. Its inhibition has been proposed as a promising new strategy to prevent bacterial pathogenicity. In this study, 827 strains from the microbiota of sea anemones and holothurians were screened for their ability to produce quorum-sensing inhibitor (QSI) compounds. The strain M3-10, identified as Vibrio alginolyticus by 16S rRNA gene sequencing, as well as ANIb and dDDH analyses, was selected for its high QSI activity. Bioassay-guided fractionation of the cell pellet extract from a fermentation broth of strain M3-10, followed by LC–MS and NMR analyses, revealed tyramine and N-acetyltyramine as the active compounds. The QS inhibitory activity of these molecules, which was confirmed using pure commercially available standards, was found to significantly inhibit Chromobacterium violaceum ATCC 12472 violacein production and virulence factors, such as pyoverdine production, as well as swarming and twitching motilities, produced by Pseudomonas aeruginosa PAO1. This constitutes the first study to screen QSI-producing strains in the microbiota of anemones and holothurians and provides an insight into the use of naturally produced QSI as a possible strategy to combat bacterial infections.

Highlights

  • The emergence of antibiotic-resistant pathogenic bacteria has become a major worldwide health concern that threatens the effectiveness of key modern medical treatments of bacterial infections and causes an increasing number of fatalities

  • The quorum-sensing inhibitor (QSI) activity of the 60 strains selected was secondly tested in an agar-plate diffusion assay using the same biosensor C. violaceum ATCC 12472, which showed that 23 strains partially or totally inhibited the production of violacein (Table 1)

  • The results indicated that the addition of the cell pellet extract of strain M3-10 reduced violacein production by 66% in C. violaceum ATCC 12472, as well as virulence factors such as biofilm formation (28%), pyoverdine production (26%), and P. aeruginosa PAO1 motility (Table 3)

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Summary

Introduction

The emergence of antibiotic-resistant pathogenic bacteria has become a major worldwide health concern that threatens the effectiveness of key modern medical treatments of bacterial infections and causes an increasing number of fatalities. This situation highlights the urgency of responding to the demand for new drugs and treatment targets [1]. The cell density-dependent mechanism, quorum sensing (QS), controls the expression of virulence genes, including virulence factors and exoenzymes, antibiotic production, as well as exopolysaccharide and biofilm formation, in many bacterial pathogens [2,3,4,5,6,7] This cell-to-cell communication coordinates the expression of certain genes in response to the accumulation and recognition of threshold concentrations of signal molecules in the surrounding medium, in addition to increases in cell density [8,9]. N-Acylhomoserine lactones (AHLs) produced by Gram-negative bacteria, oligopeptides

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