Abstract

Gram-negative bacteria like Pseudomonas aeruginosa are particularly challenging to treat due to their intrinsic multi-drug resistance (MDR) and further ability to form treatment-resistant biofilms. In 2018, the World Health Organization designated the development of novel treatments for this pathogen as a top priority in combatting MDR.¹

Researchers at McMaster have discovered that thiostrepton – an antibiotic previously considered inactive against Gram-negative bacteria – can inhibit the growth of P. aeruginosa at low molecular concentrations. They also found that thiostrepton susceptibility was inversely proportional to iron availability, suggesting that the pathways exploited by the drug have increased uptake under iron starvation. According to this mechanism, a combination of thiostrepton and FDA-approved iron chelators like deferiprone could effectively treat biofilm-forming pathogens. Further screening has confirmed that this combination also inhibits the growth of Acinetobacter baumannii, lending credence to this theory.

Applications

• The development of new therapeutics to combat infections caused by P. aeruginosa and A. baumannii.
• Potential to treat other infections caused by gram-negative bacteria that express appropriate receptors under iron-limited growth conditions.

Advantages

• Treatment of highly problematic bacterial pathogens with a class of antibiotic that was previously thought to be ineffective.

1. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, et al. (2018). Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318-327.