Quorum quenching enzymes and their effects on virulence, biofilm, and microbiomes: a review of recent advances

ABSTRACT

Introduction

Numerous bacterial behaviors are regulated by a cell-density dependent mechanism known as Quorum Sensing (QS). QS relies on communication between bacterial cells using diffusible signaling molecules known as autoinducers. QS regulates physiological processes such as metabolism, virulence, and biofilm formation. Quorum Quenching (QQ) is the inhibition of QS using chemical or enzymatic means to counteract behaviors regulated by QS.

Areas covered

We examine the main, diverse QS mechanisms present in bacterial species, with a special emphasis on AHL-mediated QS. We also discuss key in vitro and in vivo systems in which interference in QS was investigated. Additionally, we highlight promising developments, such as the substrate preference of the used enzymatic quencher, in the application of interference in QS to counter bacterial virulence.

Expert opinion

Enabled via the recent isolation of highly stable quorum quenching enzymes and/or molecular engineering efforts, the effects of the interference in QS were recently evaluated outside of the traditional model of single species culture. Signal disruption in complex microbial communities was shown to result in the disruption of complex microbial behaviors, and changes in population structures. These new findings, and future studies, may result in significant changes in the traditional views about QS.

KEYWORDS:

• Quorum sensing (QS)
• Quorum quenching (QQ)
• signaling
• lactonase
• microbiome

Article highlights

• Quorum quenching strategies can interfere with microbial signaling both in vivo and in vitro.

• Enzymatic quenchers show low diversity in substrate preference, yet the latter property is key in interference strategies.

• Highly stable and active enzymatic quenchers allow investigating signaling in complex communities.

• Interference strategies in complex communities lead to global changes in population structures and behaviors.

Declaration of interest

M Elias deposited the patent WO2014167140 A1 that was licensed to Gene&GreenTK, a company that he co-founded in 2013. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133487. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.