Science Concentrates ANTIBIOTICS
New rules for Gram-negative antibiotics Properties that allow compounds to get into and stay in Gram-negative bacteria could guide antibiotic discovery In the fight against pathogenic bacteria, Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa are particularly challenging foes. These microbes don’t respond to many common antibiotics, and no new drug active against Gram-negative bacteria has been approved in nearly a half century. Part of the difficulty in developing such antibiotics is that O molecules have a hard time slipping inside Gram-negative bacteria. The bacteria have two cell membranes, and compounds must also navigate porin protein channels to enter. A new study outlines a systematic approach to ferreting out properties compounds must have to penetrate and accumulate in Gram-negative bacteria. The authors demonstrated the power of the approach by converting an antibiotic that previously couldn’t enter Gram-negative bacteria into one that can. Paul J. Hergenrother and coworkers at the University of Illinois, Urbana-Champaign, used liquid chromatography and tandem mass spectrometry to assess the ability of compounds to enter and remain in E. coli (Nature 2017, DOI: 10.1038/nature22308). The researchers analyzed the accumulation in the bacteria of more than 180 compounds
breakthrough,” he says. “It opens up a new field—the search for comprehensive rules of compound accumulation in Gram-negative bacteria.” Until now, Lewis says, researchers have debated whether such rules from a library of modified natural products even existed, although simpler parameters they had synthesized. favoring accumulation, such as low molecA computational analysis of common ular weight and high polarity, were known properties of compounds that accumulated from previous studies. determined that the molecules must have The new findings come at a time when an unhindered amine group and should scientists have been focusing intently on Gram-negative drug discovery. The Pew Charitable Trusts and the National Institute of Allergy & Infectious Diseases held a conference on the N N N O O N O problem in February, and the National Institutes of Health has a call out for CH3 O CH3 O NH3+ grant proposals on tools to advance the discovery of therapeutics for be rigid and flattish instead of floppy and antimicrobial-resistant Gram-negative spherical. The properties of some existing bacteria. Gram-negative medications are consistent Derek Tan of Memorial Sloan Kettering with these findings. Cancer Center, whose group previously The team showed the utility of the finddeveloped a related technique to identify ings by linking an amine group (shown, red) structural properties conducive to bacterial to a ring-expanded analog of deoxynybomy- entry, comments that the new study extends cin, a rigid and flat antibacterial agent. This this type of strategy to a higher level. “It’s simple addition converted the molecule a major advance and just the beginning,” from a Gram-positive-only agent (shown, he says. “There is much more to be done left) to one that also shows efficacy against in this field.” For example, the aminated Gram-negative bacteria (shown, right). deoxynybomycin was not active in P. aerugiKim Lewis, director of the Antimicrobial nosa, suggesting the importance of further Discovery Center at Northeastern Uniexpanding the approach by analyzing traits versity, comments that additional work is controlling the ability of more molecules to still needed to determine a complete list accumulate in multiple Gram-negative speof properties. But the study “is a genuine cies, Tan says.—STU BORMAN
CHEMICAL SENSING
Improving remote detection of radioactivity After a nuclear power plant accident, for safety reasons it can be difficult for humans or even robots to get close enough to the facility to assess the situation. To get accurate information without putting people or equipment at risk, responders would benefit from better technology to sense radioactive material from afar. That could come from high-power pulsed electromagnetic waves, reports a team from Ulsan National Institute of Science & Technology (UNIST). First proposed in 2010 by the University of Maryland’s Gregory S. Nusinovich and colleagues, the approach involves using an
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C&EN | CEN.ACS.ORG | MAY 15, 2017
antenna to direct high-intensity millimeter or terahertz waves at a target area. If material there is radioactive, γ radiation or α particles ionize the surrounding air, releasing free electrons. The interaction of the antenna-directed electromagnetic waves and ionized air induces plasma formation, and the plasma in turn reflects the electromagnetic waves back to the source site for detection. The UNIST team, led by EunMi Choi, experimentally demonstrated detection of 0.5 µg of cobalt-60 from 120 cm away, the maximum distance allowed by the laboratory setup (Nat. Commun. 2017, DOI:
10.1038/ncomms15394). Off-the-shelf gyrotrons to generate the electromagnetic waves, antennae to direct them, and radiofrequency detectors could be used to deploy the technique for field detection. Depending on the equipment used, Choi believes the approach could scale to detect radioactivity at distances of at least tens of kilometers and possibly as far as 100 km. Because the time delay of plasma formation depends on γ emission energy, Choi also thinks the technique could be used to identify types of radioactive material.—JYLLIAN KEMSLEY
