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RESEARCH BRIEFS
Bacterium Wields Same Weapon Against Humans, FungiIt may be an evolutionary accident that enables a common bacterium to infect and frequently kill people with cystic fibrosis, AIDS, organ transplants, implanted devices, and severe burns. When HMS researchers pitted Pseudomonas aeruginosa against a common fungus, the bacterium appeared to attack and kill a vulnerable form of the fungus with some of the same weapons it deploys against vulnerable people.
After 24 hours together in a lab dish, Pseudomonas aeruginosa colonize and form a biofilm on the surface of fungal filaments. "We're arguing that weapons designed against fungi in the environment coincidentally make humans sick," said Deborah Hogan, HMS research fellow in microbiology and molecular genetics. The paper, published in the June 21 Science, is believed to be one of the first reports of a human pathogen using the same virulence factors that are important in human disease to fight off fungi. "Ecologically speaking, bacteria see more fungi than humans," said senior author Roberto Kolter, HMS professor of microbiology and molecular genetics. "The bacteria bind to the fungal filament, form a biofilm, and kill it. The gist of the story is, fungi are killed the same way we would be killed." In nonstressful conditions, the bacterium and the fungus Candida albicans seem to cohabitate peacefully. But under harsher conditions such as when nutrients are lacking, the yeast form of Candida can transform into filaments, which the bacteria kill. With food in short supply, the bacteria might be feeding off the fungus, Hogan speculated. The same traits that allow bacteria to cause disease in humans enable bacteria to kill fungal cells, Hogan discovered when she experimented with Pseudomonas that lacked key factors known to wreak havoc in people. Disarmed bacteria still could form biofilms on the fungal cells, but they did not kill the fungus as effectively as wild type bacteria. Conversely, bacteria that could not form biofilms could not kill the filament, showing the importance of attachment for killing. In people with compromised immune systems, both P. aeruginosa and C. albicans can cause dangerous infections. Understanding how these microbes interact may provide ideas for new therapies to defend against both bacterial and fungal assaults. --Carol Cruzan Morton
After Stroke, Chemical Reconnects BrainThe devastation caused by a stroke is not limited to the moments after the brain's blood supply cuts off or hemorrhages. For days afterward, neurons killed by the blocking or flooding of blood release toxins that can kill nearby cells. Most attempts to limit the damage after a stroke have focused on protecting neighboring neurons from this deadly aftershock. A team of HMS scientists has identified a compound that appears to rescue surviving neurons in a complementary way--by connecting them with healthy partners elsewhere in the brain. Peng Chen, Larry Benowitz, and colleagues found that rats that received a continuous infusion of the chemical inosine after suffering an artificial stroke in their motor cortex exhibited more axonal connections in the damaged areas of their brains. The animals also regained motor functions faster and more completely than rats that did not receive the compound. The findings appear in the June 24 Proceedings of the National Academy of Sciences. Because inosine is a naturally occurring chemical with few, if any, adverse side effects, Chen, a clinical fellow in surgery at Children's Hospital; Benowitz, an associate professor of neurosurgery at Children's; and colleagues believe it might provide a promising new therapeutic approach to improving function after a stroke or other brain injury. There is evidence that the brain may actually try this approach in the moments after a stroke. Inosine levels are known to rise after trauma and, according to the researchers, may contribute to the limited neuronal reorganization that occurs spontaneously after a stroke. As for how the chemical might bring about such growth, studies by the researchers have shown that inosine induces cultured neurons to express a constellation of genes associated with axon growth, including GAP-43, L1, and alpha-1 tubulin. The current study shows that GAP-43 was also elevated in certain areas of the brain of experimental animals receiving inosine.
Lead Level in Mother's Bone Linked to Child ImpairmentHigh levels of lead measured in the bones of mothers shortly after giving birth are associated with poor performance on a test of mental development in their children at two years of age, a study led by HSPH researchers has found. "Although much attention has been paid to public health efforts to reduce lead exposure in children between the ages of 6 months and 5 years..." the authors write, "less attention has been paid to understanding the transfer of lead from mother to fetus and its resulting health effects." Various methods for measuring maternal lead levels have been tried, but it has been unclear which method is most closely correlated with lead toxicity in children. The international collaborative of scientists--led by principal investigator Howard Hu, HSPH associate professor of occupational medicine in the Department of Environmental Health, and including colleagues at HMS, the U.S. National Institute of Occupational Safety and Health, and the National Institutes of Public Health and Perinatology in Mexico--has previously shown that higher maternal bone lead levels are associated with lower infant birth weight, birth length, head circumference, and rate of weight gain. In the current study, which appears in the July Pediatrics, they used x-ray fluorescence to measure lead in the tibia and trabecular (patellar) bone in 197 women within four weeks after giving birth in three Mexico City hospitals. When the children were 24 months old, the researchers administered the Bayley Scales of Infant Development (Spanish version). After adjustment of the scores for other factors that affect mental development, and for umbilical cord blood lead levels, children whose mothers scored in the lowest quartile for trabecular bone lead averaged 90.6 points on the Mental Development Index of the Bayley Scales. By comparison, children born to mothers in the second, third, and highest quartiles scored, respectively, 5.4, 7.2, and 6.5 points lower. The association with tibia lead levels was insignificant. The authors suggest that calcium supplementation, which some studies have shown to reduce bone demineralization during pregnancy, might help prevent maternal-fetal transmission of lead and its associated toxicity. --Tom Reynolds |
