Quorum sensing inhibitors: a patent review (2014–2018)

ABSTRACT

Introduction: Quorum sensing (QS) is a cell density-dependent phenomenon in which specific pathways are activated after autoinducers (AIs) outside the microorganism reach a threshold concentration. QS creates a positive feedback loop that induces a cascade of gene expression and causes biofilm formation, virulence and sporulation. QS signals are diverse, acyl-homoserine lactone (AHL), AI peptide (AIP) and AI-2 are three major categories of QS signals. QS inhibitors (QSIs) can disrupt or prevent the formation of biofilm and reduce virulence while exerting less selective pressure on the bacteria, suggesting that QSIs are potential alternatives for antibiotics.

Areas covered: This review summarized the pertinent patents on QS inhibition available from 2014 to 2018. The authors analyze these patents and provided an overview of them and their potential applications.

Expert opinion: The main strategy for QS inhibition is to use the analogues of various QS signals to block downstream signal transducers. The inactivation of signal molecules or the stimulation of the immune response is also attractive strategies to inhibit QS. However, additional clinical trials are needed to assess their efficacy in mammals. In sum, QS inhibition can reduce the virulence of bacteria without affecting their growth or killing them and the reduced pressure may minimize the increasingly resistance.

KEYWORDS:

• Quorum sensing
• inhibitor
• antibacterial
• biofilm formation
• acyl-homoserine lactones
• autoinducer peptides
• autoinducer-2

Article highlights

• This review summarized the patents concerning QS inhibition from 2014 to 2018 and gave an overview of their development and application.

• The majority of these inhibitors are based on antagonizing receptors and quenching signal molecules. Some inhibitors could also promote the immune response of the host.

• However, few clinical experiments of these inhibitors were applied assess their actual efficacy and toxicity in vivo. The mechanisms of some inhibitors are still unclear and more profound studies should be implemented in the future to unravel the exact mechanisms of the processes of QS pathway.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Reviewer disclosures

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

Additional information

Funding

This work was supported by funds from the National Key R&D Program of China, China [2018YFC0311004] and China Pharmaceutical University Initiative Program, China [CPU2018GY15].