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ANTIBIOTICS
Digging In The Dirt Yielded Novel Bacteria Fighter
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Many of the antibiotics doctors prescribe to fight bacterial infections were first unearthed as the products of microorganisms in the soil. But only about 1% of environmental microorganisms will grow in a laboratory petri dish. The other 99% are considered unculturable. Wondering what treasure trove of useful compounds might be waiting to be discovered, researchers led by biologist Kim Lewis at Northeastern University developed a screening method that coaxes unculturable bacteria to grow. Lewis and his team add small
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Researchers isolated antibacterial compound teixobactin from so-called unculturable bacteria
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amounts of bacteria to a culturing device called an iChip, place the gadget between two semipermeable membranes, and then bury it all in the soil for a week or two. Using this method, the researchers discovered the bacteria-fighting compound called teixobactin (Nature 2015, DOI: 10.1038/nature14098). The compound, a macrocyclic depsipeptide, represents a new class of bacteria fighters because it is a potent killer of gram-positive pathogens and is effective against methicillin-resistant Staphylococcus aureus and Streptococcus pneumonia in mice. Although there are a handful of new classes of antibiotics in the pipeline, the last antibiotic from a new class to be approved by FDA was Sirturo (bedaquiline), a narrow-spectrum tuberculosis fighter discovered in
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1997. Lewis’s O team reports that teixobactin’s HN NH novel mechanism of action makes it HN tough for bacteria to develop resistance to the compound. “We have sent teixobactin to a large number of laboratories, including those specifically aimed at obtaining resistant mutants. No mutants so far,” Lewis tells C&EN. The compound is currently in preclinical development with NovoBiotic Pharmaceuticals, a company that was part of the compound’s discovery.—BETHANY HALFORD
SYNTHETIC BIOLOGY
Keeping GMOs On A Leash Scientists developed methods to prevent synthetic organisms from going rogue
Genetically modified organisms are well-established workhorses in the manufacture of products as diverse as yogurt, propanediol, and insulin—applications that are confined to laboratories and factories. Yet genetically modified bacteria could one day be put to work further afield, as probiotics in our guts to fight gastrointestinal disease or as microscopic janitors to clean up oil spills. EVERTS But researchers need reliable strategies to keep the synthetic organisms on a tight leash and destroy Alive: Bacteria grown with Dead: Bacteria grown without them when their job is done to prevent them, or their synthetic amino acids build synthetic amino acids build synthetic genes, from escaping uncontrolled into the functional essential proteins truncated essential proteins environment. This year, the field of GMO biocontainment achieved several important advances. In JanuFunctional protein Nonfunctional ary, teams led by Harvard Medical School’s George protein M. Church and Yale University’s Farren J. Isaacs rewrote the DNA of Escherichia coli so that the bacterium required a synthetic amino acid—they tried several phenylalanine mimics—to produce its essential tRNA tRNA proteins (Nature 2015, DOI: 10.1038/nature14121 and tRNA tRNA 10.1038/nature14095). The life-or-death dependence of the new E. coli on synthetic amino acids would make it astronomically difficult for the GMO to surCodon vive outside the laboratory because no pool of the synthetic amino acids exists in nature. This innovasynthetic amino acid tive strategy is technically challenging to implement because researchers need to reengineer a GMO’s Engineered E. coli functions normally using a phenylalanine most essential proteins so that they rely on synthetic analog; without the synthetic amino acid, the bacterium fizzles. CEN.ACS.ORG
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ADAPTED FROM NAT U R E
amino acids. Meanwhile, earlier this month James J. Collins and colleagues at Massachusetts Institute of Technology reported an alternative leashing strategy that is potentially faster and easier to implement: two new gene circuits that can be added to GMOs as “kill switches.” These circuits ensure that GMOs grow and survive only in the presence of a certain combination of chemicals (Nat. Chem. Biol. 2015, DOI: 10.1038/nchembio.1979).—SARAH
