Phosphate Ions Alter the Binding of Daptomycin to Living Bacterial Cell Surfaces

Advancements in antibiotic drug design are often hindered by missing information on how these small molecules interact with living cells. The antibiotic, daptomycin, has found clinical success and an emerging resistance, but a comprehensive picture of its mechanism of action has remained elusive. Using a surface-specific spectroscopy technique, second harmonic generation, we are able to quantitatively assess the binding of daptomycin to living cell membranes without the addition of exogenous labels. Our results reveal similar binding affinities for both Gram-positive and Gram-negative bacteria studied, including Escherichia coli. More importantly, we show that the presence of phosphate ions influences the binding of daptomycin to the Gram-positive bacterium Enterococcus faecalis. The role of environmental phosphate has not previously been considered in any proposed mechanism, and its implications are expected to be important in vivo.

Automated summary

Using second harmonic generation, researchers found that the antibiotic daptomycin has similar binding affinities for both Gram-positive and Gram-negative bacteria, with the presence of phosphate ions influencing its binding to specific bacteria. This discovery challenges previous understanding of daptomycin's mechanism of action and is expected to be significant for antibiotic mechanisms in vivo.