NEWS OF THE WEEK HN N
N H
ANTIBIOTIC KILLING METHOD IN DISPUTE MICROBIOLOGY: Two studies cast doubt
on role of reactive oxygen species, confounding drug development
J
UST WHEN IT SEEMED that scientists had a
handle on how antibiotics kill bacteria and how their power could be amplified, new evidence has emerged that casts doubt on that approach. In 2007, James J. Collins and coworkers at Boston University presented evidence that all bacteria-killing antibiotics do their jobs by inducing the formation of reactive oxygen species (ROS) (C&EN, Sept. 10, 2007, page 8; Cell, DOI: 10.1016/j.cell.2007.06.049). The reactive molecules damage bacterial cells. The three antibiotics the Collins group used—norfloxacin (a quinolone), ampicillin (a β-lactam), and kanamycin (an aminoglycoside)—target different bacterial functions. The scientists hoped to show that a common mechanism could provide a way to make bacteria more sensitive to antibiotics. But now it seems the research results may have been too good to be true. Two studies from other research groups report that the same antibiotics used in Collins’ study don’t kill bacteria with ROS after all. Kim Lewis and coworkers at Northeastern University’s Antimicrobial Discovery Center measured ROS with hydroxyphenyl fluorescein (HPF), which was also used in Collins’ study to show that antibiotics kill bacteria with ROS. Biologists thought HPF fluoresces selectively in the presence of ROS, but Lewis and coworkers found that not to be the case. They observed that HPF lights up under anaerobic conditions, in which the formation of ROS would be impossible, and they found no correlation between HPF fluorescence and bacterial death (Science, DOI: 10.1126/science.1232688).
OH
N
S F H2N In the other study, James H O O A. Imlay and Yuanyuan Liu O N O of the University of Illinois, Norfloxacin OH Urbana-Champaign, used O several different experiments Ampicillin to determine whether antibiotics kill bacteria with ROS (Science, DOI: OH OH OH H 10.1126/science.1232751). When treating HO NH2 O O bacteria with antibiotics, they observed H no formation of hydrogen peroxide (a O O HO H2N NH2 OH hallmark of ROS), no activation of the H2N bacteria to fight oxidative damage, and OH Kanamycin no oxidation of bacterial DNA. Both the Lewis and Imlay studies show that antibiNO COMMON otics kill bacteria under ROS-hostile anaerobic condiMECHANISM? tions as well as aerobic circumstances. These antibiotics Lewis hopes both studies will bring clarity to the may not kill field of antibiotic research. “A lot of people I know bacteria by are trying to figure out the details of the mechanism inducing reactive of antibiotic killing through ROS and how that can be oxygen species exploited for potentiating antibiotic action,” he says. “I after all. think our papers will redirect the effort to something more productive.” The two studies are “thorough and together very convincing,” says Floyd E. Romesberg, who studies antibiotics at Scripps Research Institute. “Not only do they show that in general ROS are not responsible for antibiotic activity, but they also provide data and clear explanations for previously observed artifacts.” Collins, however, says the new papers are flawed. “We have serious methodological concerns about these studies, which we are addressing in a new paper that we plan to submit in the coming weeks, and we have extensive new data to include that further support our case,” he says. “We are now working to utilize this mechanism to develop effective means to enhance our existing antibiotic arsenal and treat resistant bacterial infections.” He even suggests the skeptics could be test subjects. “I am confident these therapies will work, even on the microbiologists who don’t believe in the underlying mechanism,” Collins says.—CELIA ARNAUD
ENVIRONMENT Minnesota bans purchase of soaps and cleaning products with triclosan Come June, Minnesota state agencies will be able to purchase only soaps and detergents that are free of the antibacterial ingredient triclosan. State officials say they are concerned that the chemical has been linked to endocrine disruption and the growing threat of antibiotic resistance. The move makes Minnesota the first state to adopt a procurement policy that specifically prohibits the purchase of products with triclosan, sources repre-
senting industry and environmental and health advocates tell C&EN. Some states already avoid purchasing triclosan-containing products. For instance, some state policies require the purchase of products certified by the nonprofit Green Seal, which deems products environmentally sustainable. It excludes items with triclosan. The Minnesota Pollution Control Agency says a recent study found triclosan and triclosan-derived dioxins in the sedi-
WWW.CEN-ONLINE.ORG
8
MARCH 11, 2013
ments of lakes in Minnesota that receive treated sewage (Environ. Sci. Technol., DOI: 10.1021/es3045289). “By purchasing items without triclosan, state agencies are doing their part to keep this harmful chemical out of Minnesota waters,” says Cathy Moeger, sustainability manager at the Pollution Control Agency. The state makes an exception for products with triclosan that are to be used in situations such as medical settings.—CHERYL HOGUE
