The rapid development of bacterial resistance to conventional antibiotics (such
as penicillin or vancomycin) has become a major public health concern.
Researchers have now deciphered the molecular mechanism behind selective
antimicrobial activity for a prototypical class of synthetic compounds. The
compounds, which mimic antimicrobial peptides found in biological immune
systems, function as molecular "hole punchers," punching holes in the membranes
of bacteria, according to Gerard Wong, University of Illinois researcher who
led the study.
The researchers first synthesized a prototypical class of antimicrobial
compounds, then in part used synchrotron small-angle x-ray scattering at SSRL
Beam Line 4-2 to examine the structures made by the synthetic compounds and
cell membranes.
Composed of variously shaped lipids, including some that resemble traffic
cones, the cell membrane regulates the passage of materials in and out of the
cell. In the presence of the antimicrobial molecules, the cone-shaped lipids
gather together and curl into barrel-shaped openings that puncture the
membrane. Cell death soon follows. The researchers also determined why some
compounds punch holes only in bacteria, while others kill everything within
reach, including human cells. The work is reported in a paper in the Journal of
the American Chemical Society and posted on its web site.
L. Yang, V. D. Gordon, A. Mishra, A. Som, K. R. Purdy, M. A. Davis, G. N. Tew
and G. C. L. Wong, "Synthetic Antimicrobial Oligomers Induce a
Composition-dependent Topological Transition in Membranes", J. Am. Chem.
Soc. 129, 12141 (2007)
To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/amo.html