Science Concentrates VACCINES nizing specialized receptors on bacterial cell membranes. To disrupt this process, Elizabeth M. Nolan of Massachusetts Institute of Technology, Manuela Raffatellu of the University of California, Irvine, and coworkers Agents target small-molecule iron designed and synthesized derivatives of a scavenging by Gram-negative bacteria Salmonella siderophore and conjugated it to a carrier protein that would induce an imLike Star Wars destroyers that send out Vibrio bacteria, which cause cholera (J. Med. mune response in mice (shown). Animals pods on supply missions, some bacteria Chem. 2009, DOI: 10.1021/jm900119q). immunized with the conjugates developed deploy small molecules called siderophores However, they did not evaluate the ability antibodies that recognize and sequester the to collect the essential nutrient iron from of the antibodies to protect live animals siderophores, killing Salmonella in the gut hosts they infect. Two research groups from cholera because good animal models of infected mice (Proc. Natl. Acad. Sci. USA each report vaccines that program animals’ for Vibrio infection are not available. 2016, DOI: 10.1073/pnas.1606290113). immune systems to capture siderophores, Commenting on the new studies, Harry L. T. Mobley at the University of killing invading bacteria by starving them Bergeron says the siderophore-based Michigan Medical School and coworkers of iron. immunized mice 3- with two types of The strategy could O O OO Cholera toxin become a new way Escherichia coli sidO subunit B NH to protect people erophores conjugated O O O from infections by to an immunogenic = NH O NH O O N H O O Gram-negative bactecarrier protein. These H N O O ria, which use siderosiderophore-protein O N phores. Expanding the conjugates protected Fe H HN HN arsenal against these mice against urinary O O O pathogens is an urgent tract infections (Proc. O necessity because Natl. Acad. Sci. USA Iron-chelated enterobactin (siderophore) many strains have become resistant to ex2016, DOI: 10.1073/ with polyethylene glycol linker isting antibiotics. Antibiotic vaccines are alpnas.1606324113). The ready available for conditions such as menvaccine concept “still has a ways to go.” siderophores were immunogenic enough on ingitis, Haemophilus influenzae infections, For example, some bacteria use multiple their own to elicit an immune response even pneumonia, and urinary tract infections, but siderophores, so blocking just one may not when they were not protein-conjugated. some are toxic or only weakly protective, so work for all bacteria. Nevertheless, the new Bergeron says siderophore vaccines scientists welcome new vaccine types. studies “are like absolution to us,” he says. haven’t been taken seriously enough by Seven years ago, Raymond J. Bergeron “Coupled with what we did earlier, they research funding agencies. “People will pay and coworkers at the University of Florida show that this is a credible approach.” attention now,” he says. “I hope the coninduced mice to produce antibodies against Siderophores collect iron from bacterial cept goes forward and does something for a siderophore called vibriobactin used by hosts and then bring it back home by recogpatients.”—STU BORMAN
Novel vaccines block iron
MASS SPECTROMETRY
CREDIT: ADAPTED FROM PROC. NATL. ACAD. SCI. USA
Mutagenic dyes prevalent in house dust The health hazards of brominated flame retardants lurking in household dust have made the news for years because of the ease with which humans can be exposed to the endocrine-disrupting compounds. Studies have hinted there are also large concentrations of unknown and potentially harmful brominated compounds in dust, but the number of compounds remained unclear and scientists didn’t have an efficient way to identify them, says Jianxian Sun, an environmental toxicologist at the University of Saskatchewan. Now Sun, John P. Giesy, and colleagues show that the largest class of brominated compounds in household dust by far are
azo dyes, commonly used to color clothing and furniture (Environ. Sci. Technol. 2016, DOI: 10.1021/acs.est.6b03954). The researchers took advantage of a novel screening method developed by coauthor Hui Peng. Based on ultrahigh resolution mass spectrometry combined with statistical analysis, the method can pluck individual brominated compounds out of a mixture and pinpoint their chemical formula. Out of 23 dust samples from eight homes in Saskatoon, Saskatchewan, the researchers focused on the 140 most abundant compounds identified by their method. The analysis uncovered a cluster of 78 unknown, nitrogen-rich brominated chemicals that
accounted for about 85% of the mass of brominated compounds in the dust. Closer investigation showed that one of the more common motifs among these unknowns was bromo-dinitroaniline (BNA), a raw material for the synthesis of brominated azo dyes. A standard cell-based test showed that BNA and house dust samples showed significant mutagenicity. “The results are surprising because few researchers have looked at brominated azo dyes, and it raises questions about why they haven’t been discovered before,” says Miriam L. Diamond, an environmental chemist at the University of Toronto.—JANET
PELLEY, special to C&EN NOVEMBER 14, 2016 | CEN.ACS.ORG | C&EN
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