Paper Pick #1: Vancomycin Resistance Mechanism in Bacteria

April 15, 2010 § Leave a comment

In Public Health Microbiology, BIOL 449, Dr. Butler was always telling us how the antibiotic vancomycin is considered today to be “the silver bullet” for any sort of infection.

The problem though, as we learned in class, is that there seems to be an emerging trend of bacteria which have developed resistance mechanisms against vancomycin.

Unlike most other antibiotics, which work to inhibit cell-wall building enzymes in bacteria, vancomycin works to inhibit directly cell wall synthesis by binding to the actual building blocks of the wall.  Thus, with antibiotic resistant bacteria, researchers were never sure what turned on the genes: the actual presence of the drug vancomycin, or the process of cell-wall disintegration itself.   By sticking a photoaffinity probe onto vancomycin, the researchers in this study were able to identify that the compound binding to VanS was indeed vancomycin, and that this is in effect what induces expression of resistance genes in the bacteria.

In terms of the significance of this work, lead researcher Dr. Gerry Wright, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University says:  “Out of this finding comes two different strategies to overcome drug resistance.

“Either we change the antibiotic so it doesn’t turn on the switch, or we make new compounds that block that switch and then the antibiotic works anyways.”

REFERENCE:

Kalinka Koteva, Hee-Jeon Hong, Xiao Dong Wang, Ishac Nazi, Donald Hughes, Mike J Naldrett, Mark J Buttner, & Gerard D Wright.  2010.  A vancomycin photoprobe identifies the histidine kinase VanSsc as a vancomycin receptor.  Nature Chemical Biology. Published online: 11 April 2010 | doi:10.1038/nchembio.350
<http://www.nature.com/nchembio/journal/vaop/ncurrent/pdf/nchembio.350.pdf>

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