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Archive - Jan 18, 2014

More Rigid Analogs of ADEPS Have Potent Antibiotic Activity

As concerns about bacterial resistance to antibiotics grow, researchers are racing to find new kinds of drugs to replace ones that are no longer effective. One promising new class of molecules called acyldepsipeptides — ADEPs — kills bacteria in a way that no marketed antibacterial drug does — by altering the pathway through which cells rid themselves of harmful proteins. Now, researchers from Brown University and the Massachusetts Institute of Technology have shown that giving the ADEPs more backbone can dramatically increase their biological potency. By modifying the structure of the ADEPs in ways that make them more rigid, the team prepared new ADEP analogs that are up to 1,200 times more potent than the naturally occurring molecule. A paper describing the research was published online on January 14, 2014 in the Journal of the American Chemical Society. “The work is significant because we have outlined and validated a strategy for the enhancing the potency of this promising class of antibacterial drug leads,” said Dr. Jason Sello, professor of chemistry at Brown and the paper’s senior author. “The molecules that we have synthesized are among the most potent antibacterial agents ever reported in the literature.” ADEPs kill bacteria by a mechanism that is distinct from all clinically available anti-bacterial drugs. They work by binding to a protein in bacterial cells that acts as a “cellular garbage disposal,” as Dr. Sello describes it. This barrel-shaped protein, called ClpP, breaks down proteins that are misfolded or damaged and could be harmful to the cell. However, when ClpP is bound by an ADEP, it’s no longer so selective about the proteins it degrades In essence, the binding by ADEP causes the garbage disposal to run amok and devour healthy proteins throughout the cell. For bacteria, a runaway ClpP is deadly.

Novel Biological Mechanism Relays Electrons Along Hemes in Proteins in Mineral-Breathing Bacteria

Researchers simulating how certain bacteria run electrical current through tiny molecular wires have discovered a secret that nature uses for electron travel. The results are key to understanding how the bacteria do chemistry in the ground, and will help researchers use these bacteria in microbial fuel cells, batteries, or for turning waste into electricity. Within the bacteria's protein-based wire, molecular groups called hemes communicate with each other to allow electrons to hop along the chain like stepping stones. The researchers found that evolution has set the protein up so that, generally, when the electron's drive to hop is high, the heme stepping stones are less tightly connected, like being farther apart; when the drive to hop is low, the hemes are more closely connected, like being closer together. The outcome is an even electron flow along the wire. This is the first time scientists have seen this evolutionary design principle for electron transport, the researchers reported online on January 2, 2014 in PNAS. "We were perplexed at how weak the thermodynamic driving force was between some of these hemes," said geochemist Dr. Kevin Rosso of the Department of Energy's Pacific Northwest National Laboratory. "But it turns out those pairs of hemes are essentially hugging each other. When the driving force is strong between hemes, they are only shaking hands. We've never seen this compensation scheme before, but it seems that the purpose is to allow the protein to transfer electrons with a steady flow along heme wires." Certain bacteria breathe using metal like people use oxygen. In the process, these bacteria steal electrons from carbon and ultimately transfer the electrons to metals or minerals in the ground.

Newly Discovered ATP Receptor Helps Plants Manage Environmental Change, Pests, and Wounds

ATP (adenosine triphosphate) is the main energy source inside a cell and is considered to be the high energy molecule that drives all life processes in animals, including humans. Outside the cell, membrane receptors that attract ATP drive muscle control, neurotransmission, inflammation, and development. Now, researchers at the University of Missouri (MU) have found, for the first time, the same receptor in plants and believe it to be a vital component in the way plants respond to dangers, including pests, environmental changes, and plant wounds. This discovery could lead to herbicides, fertilizers, and insect repellants that naturally work with plants to make them stronger. "Plants don't have ears to hear, fingers to feel, or eyes to see," said Dr. Gary Stacey an investigator in the MU Bond Life Sciences Center and professor of plant sciences in the College of Agriculture, Food and Natural Resources. "Plants use these chemical signals to determine if they are being preyed upon or if an environmental change is occurring that could be detrimental to the plant. We have evidence that when ATP is outside of the cell it is probably a central signal that controls the plant's ability to respond to a whole variety of stresses." Dr. Stacey and fellow researchers, graduate student Jeongmin Choi, and postdoctoral fellow Dr. Kiwamu Tanaka, screened 50,000 plants over two years to identify the ATP receptors. By isolating a key gene in the remaining plants, scientists found the receptor that aids in plant development and helps repair a plant during major events. "We believe that when a plant is wounded, ATP is released into the wound and triggers the gene expressions necessary for repair," Dr. Stacey said.

Bacterium “Breathes” Toxic Metals to Survive, Potential for Industry and Environment

Buried deep in the mud along the banks of a remote salt lake near Yosemite National Park are colonies of bacteria with an unusual property: they breathe a toxic metal to survive. Researchers from the University of Georgia discovered the bacteria on a recent field expedition to Mono Lake (image) in California, and their experiments with this unusual organism show that it may one day become a useful tool for industry and environmental protection. The bacteria use elements that are notoriously poisonous to humans, such as antimony and arsenic, in place of oxygen, an ability that lets them survive buried in the mud of a hot spring in this unique saline soda basin. "Just like humans breathe oxygen, these bacteria respire poisonous elements to survive," said Chris Abin, co-author of a paper describing the research published in the January 7, 2014 issue of Environmental Science & Technology and a doctoral candidate in microbiology. "It is particularly fond of arsenic, but it uses other related elements as well, and we think it may be possible to harness these natural abilities to make useful products out of different elements." Antimony, for example, is a naturally occurring silver-colored metal that is widely used by numerous industries to make plastics, vulcanized rubber, flame retardants, and a host of electronic components including solar cells and LEDs. To make these products, antimony must be converted into antimony trioxide, and this bacterium is capable of producing two very pure types of crystalline antimony trioxide perfectly suited for industry. Traditional chemical methods used to convert antimony ore into antimony trioxide can be expensive, time-consuming, and often create harmful byproducts.

Male Honey Bees More Susceptible Than Females to Widespread Intestinal Parasite

Gender differences in nature are common, including in humans. A research team from Bern, Switzerland has found that male European honey bees, or drones, are much more susceptible than female European honey bees, known as workers, to a fungal intestinal parasite called Nosema ceranae. Originally from Asia, Nosema ceranae has rapidly spread throughout the world in recent years, and may contribute to the high number of colony deaths now observed in many regions of the northern hemisphere. These findings demonstrate the delicate nature of male honey bees, which are important to honey bee colony reproduction, and its susceptibility to a well-distributed parasite. Honey bees are complex social organisms that demonstrate haploid-diploidy. The two female castes, workers and queens, are diploid, like humans. They contain two copies of each chromosome. Male honey bees, known as drones, on the other hand, are haploid and contain only one chromosome set. The haploid susceptibility hypothesis predicts that haploid males are more prone to disease compared to their diploid female counterparts because dominant genes on one chromosome copy have the opportunity to mask mutated genes on the other copy in diploid organisms. A research team from the Vetsuisse Faculty of the University of Bern in Switerland demonstrated in a January 17, 2014 online article in the open-access journal PLOS ONE that male honey bees are significantly more susceptible (they die sooner and have poor body condition) to an exotic fungal intestinal parasite called Nosema ceranae compared to female worker honey bees. The parasite, originally from Asia, has recently spread to have a near-global distribution during a period of high honey bee colony losses in many global regions.