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Category Archives: Biochemistry

Team discovers how bacteria resist a 'Trojan horse' antibiotic

Public release date: 19-Mar-2012 [ | E-mail | Share ]

Contact: Diana Yates diya@illinois.edu 217-333-5802 University of Illinois at Urbana-Champaign

CHAMPAIGN, lll. A new study describes how bacteria use a previously unknown means to defeat an antibiotic. The researchers found that the bacteria have modified a common "housekeeping" enzyme in a way that enables the enzyme to recognize and disarm the antibiotic.

The study appears in the Proceedings of the National Academy of Sciences.

Bacteria often engage in chemical warfare with one another, and many antibiotics used in medicine are modeled on the weapons they produce. But microbes also must protect themselves from their own toxins. The defenses they employ for protection can be acquired by other species, leading to antibiotic resistance.

The researchers focused on an enzyme, known as MccF, that they knew could disable a potent "Trojan horse" antibiotic that sneaks into cells disguised as a tasty protein meal. The bacterial antibiotic, called microcin C7 (McC7) is similar to a class of drugs used to treat bacterial infections of the skin.

"How Trojan horse antibiotics work is that the antibiotic portion is coupled to something that's fairly innocuous in this case it's a peptide," said University of Illinois biochemistry professor Satish Nair, who led the study. "So susceptible bacteria see this peptide, think of it as food and internalize it."

The meal comes at a price, however: Once the bacterial enzymes chew up the amino acid disguise, the liberated antibiotic is free to attack a key component of protein synthesis in the bacterium, Nair said.

"That is why the organisms that make this thing have to protect themselves," he said.

In previous studies, researchers had found the genes that protect some bacteria from this class of antibiotic toxins, but they didn't know how they worked. These genes code for peptidases, which normally chew up proteins (polypeptides) and lack the ability to recognize anything else.

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Study finds how bacteria resist a 'Trojan horse' antibiotic

The study appears in the Proceedings of the National Academy of Sciences.

Bacteria often engage in chemical warfare with one another, and many antibiotics used in medicine are modeled on the weapons they produce. But microbes also must protect themselves from their own toxins. The defenses they employ for protection can be acquired by other species, leading to antibiotic resistance.

The researchers focused on an enzyme, known as MccF, that they knew could disable a potent "Trojan horse" antibiotic that sneaks into cells disguised as a tasty protein meal. The bacterial antibiotic, called microcin C7 (McC7) is similar to a class of drugs used to treat bacterial infections of the skin.

"How Trojan horse antibiotics work is that the antibiotic portion is coupled to something that's fairly innocuous in this case it's a peptide," said University of Illinois biochemistry professor Satish Nair, who led the study. "So susceptible bacteria see this peptide, think of it as food and internalize it."

The meal comes at a price, however: Once the bacterial enzymes chew up the amino acid disguise, the liberated antibiotic is free to attack a key component of protein synthesis in the bacterium, Nair said.

"That is why the organisms that make this thing have to protect themselves," he said.

In previous studies, researchers had found the genes that protect some bacteria from this class of antibiotic toxins, but they didn't know how they worked. These genes code for peptidases, which normally chew up proteins (polypeptides) and lack the ability to recognize anything else.

Before the new study, "it wasn't clear how a peptidase could destroy an antibiotic," Nair said.

To get a fuller picture of the structure of the peptidase, Illinois graduate student Vinayak Agarwal crystallized MccF while it was bound to other molecules, including the antibiotic. An analysis of the structure and its interaction with the antibiotic revealed that MccF looked a lot like other enzymes in its family, but with a twist or, rather, a loop. Somehow MccF has picked up an additional loop of amino acids that it uses to recognize the antibiotic, rendering it ineffective.

"Now we know that specific amino acid residues in this loop are responsible for making this from a normal housekeeping gene into something that's capable of degrading this class of antibiotics," Nair said.

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Darwin peering through the molecular level

To Bob Rose and his colleagues, evolution isn't just a theoryit's the basis for their whole career.

"The idea of evolution is seminal to biochemistry," Rose, professor of biochemistry, said. Rose is currently working with the University, researching the gene that promotes insulin-production in various species.

"We do a lot of comparisons between species, which is very evolution-based." Rose said.

Rose is currently working on comparing the insulin promoter between humans, rats and mice in order to understand what things are conserved between the species. One of the key differences between these species is that mice have two insulin genes, whereas humans only have one.

"For some reason, the function was important enough to warrant two genes we see variations like that a lot," Rose said.

Despite those differences, enough is conserved between the proteins that regulate the genes and even the genes themselves that researchers can examine them as an important evolutionarily-preserved function.

According to Paul Wollenzien, professor of biochemistry, the first signs of evolution came at the earliest stages of life. Originally, polymers of RNA, nucleic acids that can code genetic information, self-competed for replication. Next came proteins translated from that primary genetic code, and finally life began to emerge.

Even in modern organisms, there are clues to these early events. For example, there are sequences within ribosomal RNA that are shared between the three domains of life: eukaryotes, prokaryotes and achaea. This means that the sequences were present within the progenitor of these domainsa common ancestor.

"Because we can recognize these universally-conserved sequences, we take that to mean that they were established early on in evolution," Wollenzien said. Because the sequences were established very early on, it indicates a great importance for the basic functions of life.

Evolution influences the emerging field of biochemistry with something called "Instant Evolution."

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Fielding questions about climate change

Public release date: 14-Mar-2012 [ | E-mail | Share ]

Contact: Clea Desjardins clea.desjardins@concordia.ca 514-848-2424 x5068 Concordia University

This press release is available in French.

Montreal -- Canada defines itself as a nation that stretches from coast to coast to coast. But can we keep those coasts healthy in the face of climate change? Yves Glinas, associate professor in Concordia's Department of Chemistry and Biochemistry, has found the solution in a surprising element: iron.

In a study published in Nature, Glinas along with Concordia PhD candidate Karine Lalonde and graduate Alexandre Ouellet, as well as McGill colleague Alfonso Mucci studies the chemical makeup of sediment samples from around the world ocean to show how iron oxides remove carbon dioxide from our atmosphere.

"People around the planet are fighting to reduce the amount of CO2 pumped into the atmosphere in the hopes of reducing climate change. But when it comes to getting rid of the CO2 that's already there, nature herself plays an important role," Glinas explains. CO2 is removed from the atmosphere and safely trapped on the ocean floor through a natural reaction that fixes the molecule to organic carbon on the surface of large bodies of water.

How exactly does that fixation process work? "For well over a decade, the scientific community has held onto the hypothesis that tiny clay minerals were responsible for preserving that specific fraction of organic carbon once it had sunk to the seabed," explains Mucci, whose related research was picked as one of the top 10 Scientific Discoveries of the year by Qubec Science. Through careful analysis of sediments from all over the world, Glinas and his team found that iron oxides were in fact responsible for trapping one fifth of all the organic carbon deposited on the ocean floor.

With this new knowledge comes increased concern: iron oxides are turning into what might be termed endangered molecules. As their name suggests, iron oxides can only form in the presence of oxygen, meaning that a well-oxygenated coastal ecosystem is necessary for the iron oxides to do their work in helping to remove carbon dioxide from the atmosphere. But there has been a worrying decrease in dissolved oxygen concentrations found in certain coastal environments and this trend is expanding. Locations once teeming with life are slowly becoming what are known as "dead zones" in which oxygen levels in the surface sediment are becoming increasingly depleted. That familiar culprit, man-made pollution, is behind the change.

Major rivers regularly discharge pollutants from agricultural fertilizers and human waste directly into lake and coastal environments, leading to a greater abundance of plankton. These living organisms are killed off at a greater rate and more organic carbon is sinking to the bottom waters, causing even greater consumption of dissolved oxygen. This makes the problem of low dissolved oxygen levels even worse. If the amount of oxygen in an aquatic environment decreases beyond a certain point, iron oxides stop being produced, thus robbing that environment of a large fraction of its natural ability to extract carbon dioxide from the atmosphere.

But there is hope. "This study also represents an indirect plea towards reducing the quantities of fertilizers and other nutrient-rich contaminants discharged in aquatic systems" explains Lalonde, who Glinas credits with much of the work behind this elemental study. She hopes that better understanding the iron-organic carbon stabilizing mechanism could "eventually lead to new ways of increasing the rate of organic carbon burial in sediments."

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Cool 2011 summer helped Lake Whatcom water quality a bit

BELLINGHAM - Scientific measurements of the biochemistry of Lake Whatcom showed some improvement in 2011, but that is probably the result of a cool summer, not human efforts to control polluting runoff.

So says Robin Matthews, the lead scientist on the annual lake water monitoring effort commissioned by the city. Matthews is director of the Institute for Watershed Studies at Huxley College of the Environment, Western Washington University.

"I think we got a break last summer," Matthews said.

Cold and cloudy conditions kept water temperatures lower, and that delayed and diminished the annual explosion of algae populations that have affected lake quality in previous summers.

In the hotter summer of 2009, the algae concentrations got so high that they caused a serious cut in the capacity of the city's water treatment plant, resulting in mandatory water use restrictions. But even in a cool year like 2011, the algae growth was still enough to reduce the system's capacity, Matthews said.

While the scientific measurements taken in 2011 did show a reduction in levels of phosphorus and algae, Matthews said she believes the reductions were minor, and the summer's lower temperatures probably account for those reductions.

"It (pollution measurement) is down a little but it's not down much," Matthews said. "It doesn't show an improvement from watershed changes."

Matthews refuses to draw conclusions from any single year's worth of lake water measurements. Instead, she points to the whole series of measurements going back to 1994. Those measurements show year-to-year fluctuations, but a general rising trend in both phosphorus concentrations and algae growth.

As Matthews explained it, the lake's problems stem from phosphorus-laden runoff that is made worse by human activities in the watershed. The phosphorus nourishes algae growth, and the dead algae become food for bacteria. The bacteria, in turn, deplete dissolved oxygen and make the lake less hospitable to fish.

And it becomes a vicious circle, because the lower oxygen levels result in chemical changes that release additional phosphorus from compounds and make it usable for algae food.

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Research and Markets: Biochemistry for Sport and Exercise Metabolism

DUBLIN--(BUSINESS WIRE)--

Research and Markets (http://www.researchandmarkets.com/research/b561c1/biochemistry_for_s) has announced the addition of John Wiley and Sons Ltd's new book "Biochemistry for Sport and Exercise Metabolism" to their offering.

How do our muscles produce energy for exercise and what are the underlying biochemical principles involved? These are questions that students need to be able to answer when studying for a number of sport related degrees. This can prove to be a difficult task for those with a relatively limited scientific background. Biochemistry for Sport and Exercise Metabolism addresses this problem by placing the primary emphasis on sport, and describing the relevant biochemistry within this context.

The book opens with some basic information on the subject, including an overview of energy metabolism, some key aspects of skeletal muscle structure and function, and some simple biochemical concepts. It continues by looking at the three macromolecules which provide energy and structure to skeletal muscle - carbohydrates, lipids, and protein. The last section moves beyond biochemistry to examine key aspects of metabolism - the regulation of energy production and storage. Beginning with a chapter on basic principles of regulation of metabolism it continues by exploring how metabolism is influenced during high-intensity, prolonged, and intermittent exercise by intensity, duration, and nutrition.

Key Features:

Biochemistry for Sport and Exercise Metabolism will prove invaluable to students across a range of sport-related courses, who need to get to grips with how exercise mode, intensity, duration, training status and nutritional status can all affect the regulation of energy producing pathways and, more important, apply this understanding to develop training and nutrition programmes to maximise athletic performance.

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For more information visit http://www.researchandmarkets.com/research/b561c1/biochemistry_for_s

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