The most promising member of the DARQ family was a compound called R207910.
R207910 operates in a completely different way from other known antibiotics, the findings suggest. It appears to inhibit the cell's machinery for producing energy in the form of ATP molecules. Currently there are four main classes of antibiotics, those that inhibit the bacteria's cell-wall synthesis, protein synthesis, folate biosynthesis, or nucleic acid replication.
"Our compound is very different because it's the first antibiotic to my knowledge shown to be active against any bacteria by inhibiting their energy supply. The name DARQ was invented before we identified this mechanism, but you could describe what the drug does as cutting off the energy for bacteria -- turning off the lights, you could say," Andries said.
Experiments in cell cultures showed that R207910 is potent against several different mycobacteria, including drug-resistant strains of M. tuberculosis. The drug did not target other bacteria, an advantage because less selective antibiotics can generate resistance genes in other bacterial species, and may interfere with the intestinal flora.
Next, the researchers tested their compound in mice, finding that one month of treatment with a drug cocktail that included R207910 reduced the bacterial load in the lungs to the same extent than the old cocktail did after two months. After two months, the mice's lungs seemed to be completely clear of bacteria.
These findings suggest that tuberculosis therapies including the new drug might reduce the treatment time by about 50 percent.
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Contact: Jessica Lawrence-Hurt
jlawrenc@aaas.org
1-202-326-7088
American Association for the Advancement of Science
9-Dec-2004