Tackling superbugs in their slime castles: innovative approaches against antimicrobial-resistant biofilm infections

Abstract

The rise of ‘superbugs’ like methicillin-resistant Staphylococcus aureus threatens human health on a global scale. Bacteria have established many ways to withstand antimicrobial treatments, evade the immune system and protect them from external stressors. Current medical care frequently fails to eradicate multi-drug resistant bacteria, microbial biofilms and small colony variants that can hide from antibiotic treatments inside human cells, therefore, drug discovery and drug development to improve healthcare is pivotal. In this article, novel antimicrobial strategies with extensive activity against multi-drug resistant staphylococci are described, including: Trojan Horse approaches; multi-pronged strategies; metals; repurposing of drugs; phage therapy. Preclinical validation confirmed safety and efficacy against biofilms and small colony variants in vitro and in vivo. This was the foundation for the translation of two strategies into phase I clinical trials using: (1) deferiprone and gallium-protoporphyrin to disrupt bacterial iron metabolism; and (2) colloidal silver nanoparticles as topical treatments for staphylococcal biofilm-related infections.