Alternative approaches to treat bacterial infections: targeting quorum-sensing

ABSTRACT

Introduction

The emergence of multi- and pan-drug-resistant bacteria represents a global crisis that calls for the development of alternative anti-infective strategies. These comprise anti-virulence approaches, which target pathogenicity without exerting a bacteriostatic or bactericidal effect and are claimed to reduce the development of resistance. Because in many pathogens, quorum-sensing (QS) systems control the expression of virulence factors, interference with QS, or quorum-quenching, is often proposed as a strategy with a broad anti-virulence effect.

Areas covered

We discuss the role and regulatory targets of QS control in selected Gram-positive and Gram-negative bacteria, focusing on those with clinical importance and QS control of virulence. We present the components of QS systems that form possible targets for the development of anti-virulence drugs and discuss recent research on quorum-quenching approaches to control bacterial infection.

Expert opinion

While there has been extensive research on QS systems and quorum-quenching approaches, there is a paucity of in-vivo research using adequate animal models to substantiate applicability. In-vivo research on QS blockers needs to be intensified and optimized to use clinically relevant setups, in order to underscore that such drugs can be used effectively to overcome problems associated with the treatment of severe infections by antibiotic-resistant pathogens.

KEYWORDS:

• Quorum-sensing
• anti-virulence
• quorum-quenching
• Staphylococcus aureus
• Pseudomonas aeruginosa
• biofilm

Article highlights

• Cell-density-dependent regulation (quorum-sensing) is widespread in Gram-negative and Gram-positive bacteria.

• Blocking quorum-sensing (quorum-quenching) is a frequently promoted anti-virulence approach providing a possible alternative to antibiotic therapy.

• Molecular approaches of quorum-quenching comprise direct interference with quorum-sensing signal molecules, such as by enzymatic degradation, as well as targeting their biosynthesis or receptor interaction.

• Alleged advantages of quorum-quenching include reduced development of resistance and interference with naturally existing microbiota.

• Challenges in the development of quorum-quenching for possible therapeutic application include a lack of in-vivo experimentation in appropriate animal models and differential and sometimes counterproductive roles of quorum-sensing in different bacteria and infection types.

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.

Reviewer disclosures

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

Additional information

Funding

This paper was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), US National Institutes of Health (NIH) under project number [1 ZIA AI001080].