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posted by martyb on Saturday September 15 2018, @01:28AM   Printer-friendly
from the advanced-debugging dept.

Arthur T Knackerbracket has found the following story:

Gram-negative bacteria like the Klebsiella pneumoniae... have an outer membrane that makes them impervious to many drugs, but a new compound from Genentech can breach the border and cripple them.

[...] A team led by evolutionary biologist Peter Smith at Genentech, the biotech pioneer in South San Francisco, California, began with a class of natural compounds called arylomycins. Various arylomycins can penetrate the outer membrane of gram-negatives, but they have trouble binding to their target, an enzyme embedded in the inner membrane that juts into the space between the inner and outer walls. So Smith and colleagues chemically modified an arylomycin to "systematically optimize" it such that the drug could more easily reach that space—and bind to the enzyme.

The molecule they created, dubbed G0775, was at least 500 times more potent than a naturally found arylomycin against some of the biggest gram-negative bacterial threats to humans, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. What's more, it remained potent against all 49 isolates of multidrug-resistant forms of these bacteria that the researchers obtained from patients. In a coup de grâce, when tested against a notoriously drug-resistant strain of K. pneumoniae that has defied 13 different classes of antibiotics, G0775 walloped the bacterium in lab dish experiments, they report today in Nature. "We're really excited," Smith says. "We've made the necessary changes to the molecules so that they can hit the real deal."

G0775 also showed in mice it could stymie infections from six strains of four different gram-negative bacteria. It also hasn't exhibited any potential toxicities in mammalian cells. But the road to antibiotic approval is littered with compounds that later proved toxic in larger animals or during early human trials—or that simply failed to retain their potency.

doi:10.1126/science.aav4019


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  • (Score: 0) by Anonymous Coward on Saturday September 15 2018, @11:08AM

    by Anonymous Coward on Saturday September 15 2018, @11:08AM (#735263)

    It's a "competition" the bacteria will always win, because the bacteria can mutate far faster than new drugs can be developed get regulatory approval

    FTFY