By
engineering antibacterial enzymes, Dartmouth investigators led by Karl
Griswold, PhD are using novel strategies to target the prevalent drug-resistant
bacterium Staphylococcus aureus.
Recent papers in FEMS Microbiology Letters and Applied Microbiology and
Biotechnology describe their findings from a genome mining effort seeking novel
antibacterial agents. A third paper published in ACS Chemical Biology examines
redesigned versions of human lysozyme, a broad-spectrum antibacterial enzyme.
In
the studies on Staphylococcus aureus,
Griswold's team showed that a bacteria's own molecular machinery for cell wall
synthesis and remodelling can be turned against itself. Using genetic
engineering, the enzymes can be modified such that, when applied from the
outside, they attack and kill the bacteria from which they were originally
cloned. The key is using bioinformatics to identify a bacterium’s endogenous
"autolysins," which are enzymes involved in physiological processes
such as cell division, and then leveraging molecular engineering strategies to
convert the autolysins into potent antibacterial agents.
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