Quorum Sensing

Chapter 26

Identification of AI-2 Quorum Sensing Inhibitors inVibrio

harveyiThrough Structure-Based Virtual Screening

Tianyu Jiang, Peng Zhu, Lupei Du, and Minyong Li

Abstract

Quorum sensing (QS) is a cell-to-cell communication system that regulates gene expression as a result of
the production and perception of signal molecules called autoinducers (AIs). AI-2 is a QS autoinducer
produced by both Gram-negative and Gram-positive bacteria, in which it regulates intraspecies and
interspecies communication. The identification of QS inhibitors is considered a promising strategy for
the development of anti-virulence drugs with reduced selective pressure for resistance. Here we describe a
high-throughput virtual screening approach to identify AI-2 quorum sensing inhibitors on the basis of
Vibrio harveyiLuxPQ crystal structure. Seven potent inhibitors with IC 50 values in the micromolar range
were selected with no effect or low effect onV. harveyigrowth rate.

Key wordsAI-2,Vibrio harveyi, LuxPQ, Quorum sensing inhibitors, Virtual screening

1 Introduction

Quorum sensing (QS) is a mechanism of bacterial communication

that governs gene expression in response to population density and

fluctuation in the surrounding environment. QS is based on the

production, secretion, and perception of chemical signaling mole-

cules called autoinducers [1–3]. Bacterial quorum sensing plays a

role in many biological functions, including biofilm formation,

bacterial virulence, antimicrobial resistance, antibiotic production,

competence, conjugation, swarming motility, and sporulation

[4–9]. It is believed that QS is the suitable target for antimicrobial

therapy, since QS inhibitors are likely to be applied as anti-virulence

drugs with reduced selection for resistance [10]. The main QS AIs

are acyl-homoserine lactones (AI-1), AI-2, AI-3, AI peptides, cho-

lerae autoinducer-1 (CAI-1), andPseudomonasquinolone signal

(PQS) [11–17]. AI-2 is a QS signaling molecule produced by

both Gram-negative and Gram-positive bacteria, in which it med-

iates intraspecies and interspecies communication [18–20]. Hence,

Livia Leoni and Giordano Rampioni (eds.),Quorum Sensing: Methods and Protocols, Methods in Molecular Biology,
vol. 1673,https://doi.org/10.1007/978-1-4939-7309-5_26,©Springer Science+Business Media LLC 2018

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