Novel therapeutic strategies for treating Pseudomonas aeruginosa infection

ABSTRACT

Introduction

Persistent infections caused by the superbug Pseudomonas aeruginosa and its resistance to multiple antimicrobial agents are huge threats to patients with cystic fibrosis as well as those with compromised immune systems. Multidrug-resistant P. aeruginosa has posed a major challenge to conventional antibiotics and therapeutic approaches, which show limited efficacy and cause serious side effects. The public demand for new antibiotics is enormous; yet, drug development pipelines have started to run dry with limited targets available for inventing new antibacterial drugs. Consequently, it is important to uncover potential therapeutic targets.

Areas covered

The authors review the current state of drug development strategies that are promising in terms of the development of novel and potent drugs to treat P. aeruginosa infection.

Expert opinion

The prevention of P. aeruginosa infection is increasingly challenging. Furthermore, targeting key virulence regulators has great potential for developing novel anti-P. aeruginosa drugs. Additional promising strategies include bacteriophage therapy, immunotherapies, and antimicrobial peptides. Additionally, the authors believe that in the coming years, the overall network of molecular regulatory mechanism of P. aeruginosa virulence will be fully elucidated, which will provide more novel and promising drug targets for treating P. aeruginosa infections.

KEYWORDS:

• Pseudomonas aeruginosa
• virulence
• quorum sensing
• type III secretion system
• type VI secretion system
• transcriptional regulators
• inhibitor

Article highlights

• Inhibitors targeted to QSS and its regulators have been developed to treat P. aeruginosa virulence.

• A combinatorial approach against biofilm formation is recommended.

• Interfering with T3SS and T6SS components or its key regulators is a potential strategy against P. aeruginosa infection.

• A group of virulence regulators (such as VqsM, AlgR, CdpR, RpoN, CysB, AnvM, and VqsR) are potential drug targets to inhibit P. aeruginosa virulence.

• Pyoverdine system is indispensable for virulence of P. aeruginosa in mice infection model.

• Bacteriophage, vaccine, and antimicrobial peptides are promising strategies to treat P. aeruginosa infection and biofilm formation.

Declaration of interest

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.

Referee disclosures

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

Additional information

Funding

The authors are supported by the Shenzhen Science and Technology Fund (via grant JCYJ201708118103038049) and the Health Medical Research Fund of Hong Kong (grant No. 17160022).