NEWS OF THE WEEK
BACTERIA SAY NO TO DRUGS BIOCHEMISTRY: Nitric oxide synthesis neutralizes antibiotics
M
H2N
HO
ANY SPECIES of bacteria express enzymes
that synthesize nitric oxide (NO) from arginine, but so far the physiological role of such bacterial NO synthases has been a mystery. Now, Evgeny Nudler and colleagues at New York University School of Medicine have shown that endogNH2 N+ enously produced NO protects bacteria from a broad spectrum of natural and synthetic anCH3 tibiotics (Science 2009, 325, 1380). Their results suggest that inhibiting NO synthase in disease2 NO+ + 2 H2O causing bacteria could enhance the efficacy of antimicrobial therapy. 2 N2 To determine the function of bacterial NO synthase, the researchers deleted the gene encoding the enzyme in three species of bacteria. The strains lacking NO synthase grew similarly as the OH
N+ CH3
NO+ produced by bacterial enzymes reduces the potency of the antibiotic acriflavine.
LACKING FUNDS FOR SPACE EXPLORATION
Panel finds that changes are needed at NASA for the U.S. to have a continued meaningful human exploration program. NASA
SPACE POLICY: NASA must change human exploration goals or budget, review finds
N
ASA’S human space flight program is unsustain-
able at current levels of funding, according to a summary report released on Sept. 8 by a blueribbon panel that assessed the agency’s plans for human exploration. Changes to either NASA’s goals for exploration or its annual budget are necessary, the report says. “The Committee finds that no plan compatible with the FY 2010 budget profile permits human exploration to continue in any meaningful way,” the panel states in its 12-page summary. For a human exploration program to meet its stated goals, the panel says, NASA must receive $3 billion more per year beginning with its 2010 budget, which is set in the presidential request at $18.7 billion. “In absolute terms, it’s not that much more money,” says John M. Logsdon, an emeritus professor at George Washington University’s Space Policy Institute. “But whether it is politically feasible given everything else that’s going on is a judgment” call for President Barack Obama. WWW.CEN-ONLINE.ORG
8
wild-type bacteria under normal conditions, but were more sensitive to many antibiotics of diverse cellular targets and structures, such as lactams, aminoglycosides, and quinolones. Nudler and coworkers show that NO increases the antibiotic resistance of several species of bacteria, including harmful human pathogens, by two mechanisms. First, NO+, a product of NO oxidation, directly modifies some antibiotics. Second, NO protects bacteria against oxidative stress. In addition to inhibiting specific cellular targets, many antibiotics kill bacteria by promoting the formation of cell-damaging reactive oxygen species such as hydroxyl radicals and superoxide anions. NO not only inhibits chemical reactions that produce these reactive oxygen species, but also activates two enzymes that reduce oxidative stress. The study helps explain how bacteria can coexist with microorganisms that produce natural antibiotics, says Carl Nathan, a professor of microbiology at Weill Cornell Medical College. But he notes that for therapeutic applications, NO synthase inhibitors should specifically target the bacterial enzyme while sparing mammalian NO synthases, which play important physiological roles. “It might be difficult to identify one compound that targets multiple bacterial species’ NO synthases but none of the host’s NO synthases,” he says.—LAURA CASSIDAY
The summary report provides five options for NASA’s human space exploration; two could be carried out without a budget increase with less than optimal results, and three would be possible only with additional funds. In all options, the space shuttle, which was set to retire in 2010, would continue flying until 2011. One scenario extends space shuttle flights to 2015. Under all options, the earliest that space shuttle replacements would be ready is 2016. In three of the five options, the lifetime of the International Space Station, which is nearly complete and beginning to ramp up its science activities, would be extended to 2020; the station is budgeted to operate through 2015. In response to the summary report, the White House issued a statement reaffirming the President’s commitment to human space exploration. Once the complete report is released later this month, the Administration is expected to swiftly make decisions that will be reflected in the 2011 budget cycle. In the meantime, committees in both houses of Congress are set to hold hearings on the panel’s findings this week. Because appropriations are not yet finalized for 2010, Congress can still make changes to NASA’s 2010 budget. It is unclear, however, whether they will do so or wait for the Administration to act. “The ball is squarely in President Obama’s court” when it comes to deciding the future of NASA’s human space flight program, Logsdon says.—SUSAN MORRISSEY
SEPTEMBER 14, 2009
