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First New Type of Antibiotic Discovered in 30 Years Might Be Good News


Stashed in: Science!, Medicine, Medical Breakthroughs, Microbiome

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Am I understanding that they found an antibiotic that can kill tuberculosis and staph infections?

Many of the most widely used antibiotics have come out of the dirt. Penicillin came from Penicillium, a fungus found in soil, and vancomycin came from a bacterium found in dirt. Now, researchers from Northeastern University and NovoBiotic Pharmaceuticals and their colleagues have identified a new Gram-positive bacteria-targeting antibiotic from a soil sample collected in Maine that can kill species including methicillin-resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis. Moreover, the researchers have not yet found any bacteria that are resistant to the antibiotic, called teixobactin. Their results are published today (January 7) in Nature.

...

That the antibiotic can kill M. tuberclosis “is a major breakthrough because it is virtually certain to be effective for the multi-resistant strains that are now all but impossible to treat,” said Richard Novick, a microbiologist at New York University Langone Medical Center who was not involved in the work.

Although further studies are needed before the antibiotic can be tested in humans, animal efficacy models are often predictive of a drug’s effects in humans, said Gerard Wright, director of the Institute for Infectious Disease Research at McMaster University in Hamilton, Canada, who penned an accompanyingeditorial.

One of those Reddit comments offers a good explanation:

Here's the paper: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature14098.html

The important thing about this is the way the new antibiotic, Teixobactin, was found... One new antibiotic is nice but only goes so far.... a system that can repeatedly produce new antibiotics in a turn-key fashion is MUCH more useful.

The OP's article doesn't really explain well how this was found and why it falls into that turn-key repeatable class of operations, but I can fill that in. The key thing to note is the fact that one of the authors of the Teixobactin paper is Slava Epstein. Slava Epstein is someday going to get a Nobel prize. This is because of the fact that he has solved the culture problem... the fact that most organisms won't grow in a petri dish.

The way he did this is pretty cool: He realized that it wasn't that they COULDN'T grow in the lab, it's that they WOULDN'T grow. Bacteria, like most organisms, take cues from their environment: for example a bear doesn't intrinsically know when winter is coming, rather he sees the leaves change, and the birds flying south and from this data (that predominantly originates from other organisms) knows when it's time to get ready to hibernate. Likewise, bacteria collect information from their environment in the form of soluble molecules, mostly produced by other micro-organisms, to know when it's a good bet for crucial biological processes such as cell-division... if they don't get those signals, then they don't divide. Since the other organisms providing those signals do not exist in the otherwise sterile petri-dishes in a laboratory... they won't divide there.

So, what Slava Epstein's lab did was that they collected bacterial cells from the soil, suspended them in a lump of agarose (basically gelatin) called a "plug", and then surrounded that agarose plug with a semi-permeable membrane which would not let cells through, but would let small molecules through, and then put the whole thing back into the soil that the bacteria were first removed from. Because the small molecules of the environment can enter this agarose plug, the cells suspended there know to divide. When the agarose plug is later retrieved there are colonies of bacteria growing there.... but this is just the beginning. Each of these colonies is composed of many cells that are all descended from a single bacteria that would grow in the soil environment but not the lab. Slava Epstein's people then collected cells from such a colony, those cells were then placed into two new agarose plugs. One of those new plugs was placed back into the soil, and one into an incubator in the lab. Of course the cells in the soil plug grow since they are getting whatever signalling molecules they need from whatever else is in the soil. But there's a chance that the incubator cells will grow too... the reason is that the more you grow the cells, the more you select for UNCONDITIONAL growth. That is, as the cells divide, mutations will naturally occur and eventually a mutation will occur that causes the cell to stop looking for whatever signal(s) it normally needs in the environment in order to unlock growth. Some times this is a easy mutation to arise, and sometimes it takes many dozens of rounds of harvesting colonies from soil-agarose-plugs... but it's just a matter of time eventually evolution will work and the selective pressures created by this system will force an unconditional growth phenotype. The final result is a previously ungrowable bacteria that is now domesticated and growable in the lab. Once you have that, you can test it for the production of useful products such as antibiotics. Want to test more products? No big deal, just repeat he above system with more organisms... since there's a near unlimited and unique diversity of micro organisms in every single cubic foot of dirt, you'll basically never run out.

Of course, in the long run, synthetic biology techniques that allow us to bypass messing with growing the source organisms for such products and just skip ahead to the products themselves by sequencing DNA from single cells and then synthesizing the interesting parts of that DNA that encode for products (called "biosynthetic clusters") and then expressing them in already convenient laboratory or industrial microorganisms. But the bacteria domestication approach is still important for several reasons: It proves the underlying thesis that the reason we had "run out" of antibiotics wasn't that there aren't more, but merely because we were only looking in same very small space over and over again. Also, many of these interesting gene products, like antibiotics, must be synthesized from metabolic intermediates that are not universally in all bacteria. That makes the domestication approach faster to produce products of interest in the short term. However, in the next 10-15 years look to see the synthetic biology world creating chassis organisms with interchangeable metabolisms to address this.

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