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29 February 2008

  Scientists Decipher Mechanism behind Antimicrobial "Hole Punchers"

—from a University of Illinois Urbana-Champaign press release


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)

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