Newfound hijacked proteins linked to salmonella virulence

Scientists have discovered that bacteria like E. coli and Salmonella have a sneaky way of making minor alterations to their genes to boost their chances for infection.

It's a fascinating discovery made at Ohio State University, which is featured in the Aug. 14 issue of Nature Chemical Biology. This discovery shows how bacteria make tweaks in their genes, and their proteins to gain strength.

The team includes research scientist Herve Roy, who joined the University of Central Florida faculty at the College of Medicine this month. He co-authored the paper after conducting research in OSU Professor Michael Ibba's lab.

"Mother Nature tinkers a lot," Roy said from his new lab in Orlando. "Our recent findings illustrate that new proteins in living organisms often evolve from older pre-existing ones, and that evolution updates biochemical mechanisms of living cells by tweaking them a little by applying molecular patches."

The precise role of one protein in bacteria, EF-P, remains a mystery, but this team found that it plays an essential role in the virulence of Salmonella enterica typhimurium, a common foodborne pathogen causing diarrhea, fever, and abdominal cramps, and occasionally lifetime chronic arthritis. Salmonella also accounts for about 400 deaths each year in the United States.

EF-P is known to play a role in protein biosynthesis, which is a keystone mechanism present in all organisms. This process is the chain assembly line that decodes the blue prints stored in the genomes of living organisms, to make all the proteins necessary to sustain life.

The team's research identified a modification born by EF-P that acts as a molecular patch on protein synthesis. The patch seems to increase the bacteria's prowess. Interestingly, the modification on EF-P is made by a hijacked protein, normally involved in the protein synthesis machinery itself.

In the Aug. 14 issue of Nature Chemical Biology, Roy and co-authors identified the chemical nature of the modification that occurs on EF-P. This is critical because in the team's experiments, when the modified version of EF-P is absent, Salmonella doesn't spread.

Because the mechanism by which the modification occurs is unique to bacteria and this system is involved in virulence it could be a potential drug target, Ibba said.

Roy's experience and interest in this area is what drew him to UCF. His lab in the Burnett School of Biomedical Sciences at UCF will use National Institutes of Health funding to explore how some other components of the protein synthesis machinery have been hijacked to accomplish alternate cellular processes. For instance, one process utilizes parts of the protein synthesis machinery to modify components of the bacterial membrane. This mechanism increases bacterial resistance to a large spectrum of antibiotics and presents a good avenue for new drugs that could potentially alleviate or cure many infectious diseases.

"That's why I came to UCF," Roy said. "There is a good team of scientists here working in infectious diseases. There is a good opportunity to collaborate and make a difference."

Provided by University of Central Florida (news : web)

Concerns about efforts to foster the biofuel boom

Despite growing evidence that biofuels may not be the cure-all once envisioned, many countries are still rushing headlong with biofuels development policies that experts say are having negative as well as positive impacts on the sustainable-energy dream. That's the topic of the cover story in the current edition of Chemical & Engineering News (C&EN), ACS' weekly newsmagazine.

In the article, C&EN Contributing Editor Rajendrani Mukhopadhyay points out that belief in biofuels' ability to supply fuel for cars and trucks dates to 1925, when automobile pioneer Henry Ford predicted that plants would be the transportation fuel-of-the-future. That prediction became enshrined in government policies over the last decade as the United States and more than 50 other countries began efforts to integrate biofuels into the fuel supply.

"Producing fuel crops that would meet a country's domestic fuel needs, revitalize rural economies, and cut down on greenhouse gas emissions appeared to be a one-size-fits-all solution," the article states. With scientific research and practical experience, a more realistic view of biofuels' potential has emerged. With it come concerns about government policies involving use of corn and other food crops for biofuel production, for instance, and the environmental impact of the biofuel industry.

More information: "Examining Biofuels Policy": http://pubs.acs.or … 33cover.html

Provided by American Chemical Society (news : web)

Virus uses 'Swiss Army knife' protein to cause infection

 In an advance in understanding Mother Nature's copy machines, motors, assembly lines and other biological nano-machines, scientists are describing how a multipurpose protein on the tail of a virus bores into bacteria like a drill bit, clears the shavings out of the hole and enlarges the hole. They report on the "Swiss Army Knife" protein, which enables the virus to pump its genetic material into and thus infect bacteria, in the Journal of the American Chemical Society.

Akio Kitao and colleagues focus on a group of viruses termed "bacteriophages," which literally means "bacteria eaters." These viruses infect bacteria like E. coli and usually make the bacteria dissolve. Infection involves injecting their own DNA or RNA into the bacteria, so that the viral genetic material takes over control of the bacteria. The tools for doing so are among numerous invisible nanomachines — so small that 50,000 would fit across the width of a human hair —that work unnoticed in organisms ranging from microbes to people.

The scientists recreated intricate details of the protein's work as it helps the tail of the virus infect E. coli bacteria. Their computer models show that the protein performs tasks in a regular sequence, starting with a screw-like motion as it begins to penetrate the outer membrane of E. coli. The protein acts as a cell-puncturing bit, a pipe to draw away membrane debris and a tool to enlarge the puncture hole, among other functions. The infection process demonstrates "a case where a single-function protein acquired multiple chemical functions" as different parts of its structure come in contact with bacterial membrane proteins.

More information: “Screw motion regulates multiple functions of T4 phage protein gp5 during cell puncturing” J. Am. Chem. Soc., Article ASAP
DOI: 10.1021/ja204451g

Abstract
Bacteriophage T4 penetrates the outer membrane of Escherichia coli using a multifunctional device composed of a gene product 5 (gp5) protein trimer. We report that gp5 sequentially exerts distinct functions along the course of penetration stages induced by screw motion. A triple-stranded ß-helix of gp5 acts as a cell-puncturing drill bit to make a hole on the membrane and then send the lipids upward efficiently by strong charge interactions. The gp5 lysozyme domains, which degrade the peptidoglycan layer later, are shown to play novel roles to enlarge the hole and control the release of the ß-helix. The lysozyme active site is protected from lipid binding during the penetration and is exposed after the ß-helix release. Intrinsic multiple functions of gp5 are shown to be served in turn regulated by gradual change of interdomain interactions, which enables the initial infection process with single protein trimer by continuous screw motion. The results of lysozyme domain should be understood as the case where a single-function protein acquired multiple chemical functions through interplay with other domains in a multidomain protein.

Provided by American Chemical Society (news : web)

Nature reaches for the high-hanging fruit

In the first study of its kind, researchers have used tools of paleontology to gain new insights into the diversity of natural plant chemicals. They have shown that during the evolution of these compounds nature doesn't settle for the 'low-hanging fruit' but favours rarer, harder to synthesise forms, giving pointers that will help in the search for potent new drugs.

Research on the fossil record has allowed the study of the evolution of the characteristic swirl shapes of Nautilus shells and shown that recurrent designs have formed to cope with changing sea levels. Why these forms occur, and not others, is an important evolutionary question, and to answer this, an analytical technique known as theoretical morphology has been developed. Theoretical morphology involves the mathematical simulation of forms such as the possible shape and dimensions of the nautilus shell. This allows a comparison of theoretical and actual distributions to study the evolutionary significance of biological forms, past and present.

Inspired by this, a group of scientists led by Dr Paul ÓMáille at the John Innes Centre and the Institute of Food Research, which are strategically funded by BBSRC, and Joseph P. Noel at the Salk Institute / Howard Hughes Medical Institute where the work began, applied the same theoretical morphology techniques to the study of terpenes, a group of natural products produced by plants.

Plants like pepper, tomato, and potato belong to the Solonanceae family, and they synthesize a signature set of terpenes for chemical defense against pathogens. Terpenes are essential for the ecological viability of the plant but also provide important compounds for human use including pharmaceuticals. Examples of well-known bioactive terpenes include taxol, which is used to treat certain cancers, and the anti-malarial drug artemisinin. Terpenes are useful as fragrances and flavourings, and their diverse uses have made them the subject of much research looking for novel compounds.

"The big question is how plants have evolved to make these chemicals," said Dr ÓMáille. "Is there a physical explanation, based on the chemical reaction, for why certain terpenes are favoured? Are plants simply making the easy to synthesize low hanging fruit of the terpene chemical world?"

To investigate these questions, Dr ÓMáille, Professor B. Andes Hess of Vanderbilt University and colleagues applied theoretical morphology to quantum mechanics calculations to compare theoretical and actual abundances of terpenes from solanaceaous plants. "We discovered a perplexing disparity between the predicted and natural abundance of terpenes. The common terpenes we see in nature are predicted to be quite rare, based on the chemistry. On the other hand, the terpene forms predicted to dominate are scarcely seen in nature." said Dr ÓMáille.

"Nature in fact reaches for the higher-hanging fruit, skewing chemical reactions to favour rarer chemicals. This suggests an adaptive significance to the distribution of chemicals produced by plants."

The distribution and diversity of plant terpenes in nature has yet to be exhaustively characterized, however this study provides new insights into the physical processes that underlie terpene biosynthesis in plants. This may reveal routes to rare or undiscovered natural products with potent bioactivities that could be used to help meet the ever-growing demand for new effective drugs.

More information: Physical constraints on sesquiterpene diversity arising from cyclization of the eudesm-5-yl carbocation, Journal of the American Chemical Society 133(32), 12632. doi: 10.1021/ja203342p

Provided by John Innes Centre

Alligator fat could be used to make biodiesel

 In addition to being a novelty food, alligators could also provide a feedstock for biodiesel. Every year, the alligator meat industry disposes of about 15 million pounds of alligator fat in landfills. Now scientists have found that oil can be extracted from the fat and used to make a high-quality biodiesel.

The researchers, Rakesh Bajpai and coauthors from the University of Louisiana, have published their study on the possibility of using alligator fat as fuel in a recent issue of the American Chemical Society journal Industrial & Engineering Chemistry Research.

In 2008, the US produced about 700 million gallons of biodiesel to help supply some of the 45 billion gallons of diesel consumed that year. Most of the biodiesel came from soybean oil. Due to concerns that using food crops to produce fuels will raise the price of food, scientists have been investigating alternative feedstocks, including sewage sludge, Chinese tallow, and used vegetable oil.

By showing in experiments that oil extracted from alligator fat meets nearly all of the official standards for high-quality biodiesel, the Louisiana researchers have added another feedstock to the list. The scientists explained that alligator fat has a high lipid content, and the lipids could be recovered by microwaving frozen samples and by using a chemical solvent.

Although it would play a small role in biodiesel production if it is ever to be used, alligator fat could have an advantage of lower processing costs compared to some other feedstocks since it is a waste product.

More information: Potential of Alligator Fat as Source of Lipids for Biodiesel Production, Ind. Eng. Chem. Res., Article ASAP, DOI: 10.1021/ie201000s

Abstract
A large amount of alligator fat (AF) is produced by alligator meat processing industry and disposed in landfills or discarded as waste. The AF can be used as a potential feedstock for biodiesel production due to its high lipid content. In this work, recovery of lipids from the AF tissue was studied by solvent extraction as well as by microwave rendering. Microwave rendering resulted in AF oil recovery of 61% by weight of the frozen AF tissue obtained from producers. The fatty acid profile of the lipid showed that palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) were the dominant fatty acids accounting for 89–92% of all lipids by mass; 30% of the fatty acids were saturated and 70% were unsaturated. The biodiesel produced from AF oil was found to meet the ASTM specifications of biodiesel concerning kinematic viscosity, sulfur, free and total glycerin, flash point, cloud point, and acid number.

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