In one of the first demonstrations of the practical value of systems biology, James Collins and his colleagues at Boston University in Massachusetts have shown how the aminoglycoside class of antibiotics works. Although it was known that these compounds disrupt ribosomes — the cell's protein-making machinery — and cause proteins to be wrongly made, exactly how this killed bacteria was unclear.
Using DNA microarrays, Collins and his team mapped out changes in the gene-expression patterns of Escherichia coli treated with one or other of the aminoglycosides gentamicin and kanamycin. This allowed the researchers to pin down the gene networks that the drugs influenced. From these data and studies with bacterial mutants, they worked out that the movement of certain defective membrane proteins creates an electrochemical gradient across cell membranes that ultimately spawns harmful hydroxyl free radicals.