posted on 2021-10-15, 11:26authored byLindsey
N. Miller, Marea J. Blake, Eleanor F. Page, Hannah B. Castillo, Tessa R. Calhoun
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.