Shaky sensor. A cantilever (c) covered by bacteria (b) shakes up and down as the bacteria metabolize on its surface, and the vibrations are detected by a laser beam
(left) Sandor Kasas. (Right) and Sandor Kasas Giovanni Longo
For much of the last decade, a Boston research team eagerly exhumed and reburied dirt. This is part of a strategy to reach an untapped source of new antibiotic-estimated 99% of the microbes in the environment who refuse to grow in laboratories. Now their technique gave a promising: a previously unknown bacterium that is a compound having infection-killing capabilities. In addition, the team claims in a report today, the compound is unlikely to fall in the problem of antibiotic resistance. This suggestion has its skeptics, but if the drug is in clinical trials, it would be an indispensable weapon against several increasingly difficult to treat infections.
Many existing antibiotics, including penicillin, have been identified by culture naturally occurring microorganisms-bacteria often try to kill each other with chemical warfare, it is. But the supply of new microbes that grow in a laboratory has been widely exploited on. In 02, microbiologist Kim Lewis, and his colleague at Northeastern University in Boston, environmental microbial Slava Epstein, described a new technique for coaxing bacteria to grow: Put soil samples in tiny rooms sandwiched between permeable membranes and return these items to the ground. The bacterial strains confined in rooms form colonies, partly because the suspects of the team, to growth factors from organisms that pass through neighboring membranes. The resulting colony "domesticated" can then be removed from the chamber and sometimes be more easily call a Petri dish of home.
The researchers used a version of this approach to isolate and develop new colonies-many bacteria in soil dug in the courtyard of microbiologist Losee Ling, who heads the research and development of startup business NovoBiotic Pharmaceuticals, formed to commercialize their approach. To test the antibacterial properties of the soil microbes, the team that each duel in a laboratory dish with S taphylococcus aureus , a cause of skin and severe respiratory infections. They then isolated and tested individual 10,000-compounds in all bacteria that killed the staph bacteria more effectively.
A bacterium, a field of grass in Maine, produced a compound with powerful abilities to kill a variety of other bacterial species, including many human pathogens. In addition, these pathogens have failed to develop resistance to the compound: There were no survivors individuals who had evolved to resist his attack. (Resistance usually develops when a small percentage of microbes evade antibiotic due to a mutation, then the bacteria multiply.) Lewis was initially taken this as a sign of total devastation it discourage brand "another detergent boring. "(Bleach, after all, is a strong antibiotic, but it is a little too effective in killing surrounding cells.) However, it appeared that the new compound, whose group named teixobactin, was not toxic to human cells in a dish.
and he showed other qualities of a good antibiotic, online team reports in Nature . on the growth of bacteria in lab dishes, he outclassed vancomycin, a long-drug invoked to treat stubborn methicillin-resistant S taphylococcus aureus (MRSA), by a factor 100, Lewis said. In mice infected with MRSA , teixobactin injections leads to a survival rate of 100% at lower doses than vancomycin.
The compound is effective against the so-called Gram-negative bacteria, increasingly feared in hospitals for their resistance to existing drugs. But the authors suggest that it may be of great value for people who are fighting MRSA, tuberculosis and infections with Enterococcus rare bacterial strains but-villain who do not respond to available drugs.
These results offer hope that other promising agents waiting to be discovered in the ground, said Helen Zgurskaya, a biochemist at the University of Oklahoma, Norman, who studies how bacteria become antibiotic sensitive. "This study demonstrates that non-culturable bacteria ... have new previously unrecognized biologically active compounds ,,," she said. "We now have proof of principle, and I hope more people will follow suit . "
But will teixobactin, like so many promising agents before finally reaching his match in a resistant strain? Lewis and his co-authors believe that it is unlikely. Employees of the University of Bonn in Germany teixobactin understood that works by interfering with two important lipids that bacteria use to build their cell walls. (Some other known compounds function similarly, including vancomycin). The authors suggest that the bacteria are not likely to change means to resist teixobactin because it acts on two different targets that are highly conserved in many bacterial species and are not easy to change.
The bacteria eventually develop resistance to vancomycin, but Lewis points out that it took 30 years. And he thinks that this compound may have even better chances than vancomycin. Based on soil screens of the team, the compound appears to be relatively rare, so Lewis doubt that many bacteria have evolved to produce an enzyme that could destroy it.
This is a logical argument says Michael Fischbach, a microbiologist at the University of California, San Francisco. But there are many ways to develop resistance, and if any bacteria there is one substance with limited activity against teixobactin, which could be "the starting point of evolution," he said. "The results they obtained were promising, no doubt about it," he says, but "I would never underestimate the wiliness of bacteria."
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