Potential Strategies for the Eradication of Multidrug-Resistant Gram-Negative Bacterial Infections

Abstract

Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections.

KEYWORDS:

• antibiotic resistance
• antimicrobial peptides
• efflux pumps
• Gram-negative
• lipopolysaccharide
• nosocomial
• nanomaterial
• outer membrane
• polymyxin
• porins

Financial & competing interests disclosure

G Laverty acknowledges funding provided by the Queen's University Research Support Package for New Academic Staff and a Royal Society Research Grant (RG150171). 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.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

G Laverty acknowledges funding provided by the Queen's University Research Support Package for New Academic Staff and a Royal Society Research Grant (RG150171). 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.