Water-soluble cranberry extract inhibits Vibrio cholerae biofilm formation possibly through modulating the second messenger 3', 5' - Cyclic diguanylate level.

Daniel B Pederson,Min Cao,Yuqing Dong,Sara V Smith,Levi B Blue,Herman Sintim

doi:10.1371/journal.pone.0207056

Abstract

Quorum sensing (QS) and nucleotide-based second messengers are vital signaling systems that regulate bacterial physiology in response to changing environments. Disrupting bacterial signal transduction is a promising direction to combat infectious diseases, and QS and the second messengers are undoubtedly potential targets. In Vibrio cholerae, both QS and the second messenger 3’, 5’—cyclic diguanylate (c-di-GMP) play a central role in controlling motility, motile-to-sessile life transition, and virulence. In this study, we found that water-soluble extract from the North American cranberry could significantly inhibit V. cholerae biofilm formation during the development/maturation stage by reducing the biofilm matrix production and secretion. The anti-biofilm effect by water-soluble cranberry extract was possibly through modulating the intracellular c-di-GMP level and was independent of QS and the QS master regulator HapR. Our results suggest an opportunity to explore more functional foods to fight stubborn infections through interference with the bacterial signaling systems.

Highlights

Quorum sensing (QS) and the nucleotide-based second messengers, especially the cyclic dinucleotides, are two central signaling systems utilized by many bacteria to regulate their physiological functions in response to changing environmental conditions or during the developmental process
We found that low concentration of water-soluble cranberry extract standardized to 4.0% proanthocyanidins (WCESP) could significantly impede V. cholerae biofilm formation during the development/maturation stage; this inhibition is independent of the QS pathway but is possibly through modulating the intracellular c-di-GMP level
WCESP was added into the growth medium at the same time during inoculation to reach a final concentration of 2 mg/ml

Summary

Introduction

Quorum sensing (QS) and the nucleotide-based second messengers, especially the cyclic dinucleotides, are two central signaling systems utilized by many bacteria to regulate their physiological functions in response to changing environmental conditions or during the developmental process. Due to their decisive roles in bacterial physiology, QS and the second messengers have been considered as potential targets for new drug development to tackle the increasingly grim situation of antibiotic resistance. By blocking the signaling transduction rather than targeting the essential genes, placing selective pressure on resistant strains of bacteria is avoided.

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