Variable Susceptibility to Gallium Compounds of Major Cystic Fibrosis Pathogens

The decreasing efficacy of existing antibiotics against pulmonary pathogens that affect cystic fibrosis (CF) patients calls for the development of novel antimicrobials. Iron uptake and metabolism are vital processes for bacteria, hence potential therapeutic targets. Gallium [Ga(III)] is a ferric ironmimetic that inhibits bacterial growth by disrupting iron uptake and metabolism. In this work we evaluate the efficacy of three collection of CF pathogens using both reference media and media mimicking biological fluids. All CF pathogens, except Streptococcus pneumoniae, were susceptible to at least one Ga(III) compound. Notably, Mycobacterium abscessus and Stenotrophomonas maltophilia were susceptible to all Ga(III) compounds. Achromobacter xylosoxidans, Burkholderia cepacia complex, and Pseudomonas aeruginosa were more susceptible to GaN and GaM, whereas Staphylococcus aureus and Haemophilus influenzae were more sensitive to GaPPIX. The results of this study support the development of Ga(III)-based therapy as a broad-spectrum strategy to treat CF lung infections.

Automated summary

Iron uptake and metabolism are vital for bacterial growth, making gallium (III) a potential therapeutic agent that disrupts these processes and inhibits bacterial growth. Different CF pathogens showed varying susceptibility to gallium (III) compounds, with some being sensitive to all compounds while others were only susceptible to specific ones. The results support the development of gallium (III)-based therapy as a broad-spectrum strategy to treat CF lung infections.