Masses of immune cells that form as a hallmark of tuberculosis (TB) have long been thought to be the body’s way of trying to protect itself by literally walling off the bacteria.  But a new study in the January 9th issue of the journal Cell, a Cell Press publication, offers evidence that the TB bacteria actually sends signals that encourage the growth of those organized granuloma structures, and for good reason: each granuloma serves as a kind of hub for the infectious bugs in the early stages of infection, allowing them to expand further and spread throughout the body.

” This fundamentally turns our understanding of granulomas all topsy turvy,” said Lalita Ramakrishnan of the University of Washington, Seattle.  “Scientists thought they were protective, but they are not—at least not in early infection.  The bacteria use them to reproduce and disseminate themselves.”

Not only do the bacteria expand themselves within the first granuloma to form, she added, but some of the immune cells in that initial mass leave to start new granulomas elsewhere.  Those new granulomas then also serve as breeding grounds for the bacteria.

The finding suggests a new avenue for TB therapy at an important time in the struggle against TB infection.  “We might think about ways to prevent granulomas that might be therapeutic,” Ramakrishnan said.  That might be done either by intercepting the bacterial signal that spurs granulomas’ formation or by manipulating the human immune system in some other way.

” Finding a new way to intervene in the infection is particularly relevant now because there is a horrible epidemic of drug-resistant TB,” she added.  “Many of the bugs are resistant to practically everything.”

At the outset of human pulmonary tuberculosis, the inhaled bacteria (Mycobacterium tuberculosis) is gobbled up by immune cells known as macrophages and transported into the lung.  There, infected macrophages recruit additional macrophages and other immune cells to form granulomas.  Under the classical view, those granulomas help protect against the bacteria, even if they don’t successfully contain the infection.  They were also thought to form only after the adaptive immune system shifts into gear.

But Ramakrishnan’s team began to find evidence calling that classical view into question by studying the disease in zebrafish embryos.  Because zebrafish embryos are transparent, they allowed the team to literally watch the infection take hold and spread in real time.

Their initial studies showed that, contrary to the classical view, granulomas form well before adaptive immunity comes into play, within days of infection.  Indeed, granulomas’ formation coincides with the bacteria’s expansion.  In addition, in embryonic fish infected with a less-virulent, mutant strain of bacteria, which lacked a secretion system known as ESX-1/RD1, granulomas didn’t form nearly as well.  Together, those findings suggested to Ramakrishnan’s team that granuloma formation actually works not as a protective maneuver on the part of the infected host, but rather as a bacterial tool for expanding infection.

To further investigate in the new study, the researchers observed and quantified the events in zebrafish embryos infected with normal TB bacteria and the mutant bacteria lacking the ESX-1/RD1 system.  They found that, once transported inside of cells by macrophages, the bacteria use the RD1 signal to call on new macrophages to come and move in to the growing granuloma.  As multiple macrophages arrive, they efficiently find and consume infected and dying macrophages to become infected themselves.  That process leads to a rapid, iterative expansion of infected macrophages and thereby bacterial numbers, they report.  The primary granuloma also seeds secondary granulomas as infected macrophages leave for other parts of the body.

” In summary,” the researchers wrote, “we propose that the pathway of granuloma formation and subsequent bacterial dissemination is based upon macrophage responses that are of themselves generally protective and that work reasonably well against less virulent (i.e., RD1-deficient) infection.  Rather than block these host responses, RD1-competent mycobacteria appear to accelerate them to turn the granuloma response into an effective tool for pathogenesis.  The initiation of the adaptive immune response then may halt bacterial expansion not by forming granulomas as suggested by the classical model but by altering the early granuloma into a form of stalemate between host and pathogen.”

When it comes to the decision to wake up and grow, bacterial spores “listen in” to find out what their neighbors are doing and then they follow the crowd, according to a new report in the October 31st issue of the journal Cell, a Cell Press publication.  Although there is still a lot to learn about how this process works, the discovery could lead to a new kind of antimicrobial agent that works not by killing active bacteria, but by keeping dormant bacteria—which typically resist traditional antibiotics—inactive.

The researchers show that the spores of a soil-dwelling bacteria can sense the presence of so-called muropeptide fragments released from the cell walls of other growing bacteria.  Those muropeptides act as powerful germinants, stimulating the spores to exit the safety of their dormant state and make a go of it.

As other bacteria, including those responsible for diseases like tuberculosis and staph infection, harbor a version of the receptor responsible for this ability in the bacteria under study, the researchers said they think the mechanism they’ve uncovered will prove to be universal.

“[From the bacteria’s perspective,] dormancy is a great state,” said Jonathan Dworkin of Columbia University.  “They are invulnerable to antibiotics.  If you keep them in that state, you can’t kill them but they don’t grow either.  Antibiotics usually kill bacteria by preventing some essential process, but if an antibiotic instead kept dormant bacteria from emerging, it would be essentially like killing them.”  They’d be stuck in a state of suspended animation.

In the new study, the researchers found that muropeptides derived from cultures of growing cells stimulate the germination of dormant Bacillus subtilis spores.  Diverse bacteria can serve as the source for those muropeptide molecules, but the key is a single amino acid ingredient, they found.

The spores ability to receive the signal depends on a eukaryotic-like Ser/Thr membrane kinase receptor (PrkC).  Indeed, a small molecule known to stimulate related kinases is sufficient to spark the activity of the sleeping spores.  Another small molecule called staurosporine, which inhibits related kinases, also prevents spores from activating in the presence of muropeptide.

Dworkin noted that the immune systems of animals recognize the presence of foreign invaders in a similar way, by detecting chains of muropeptide (called peptidoglycans).

” The recognition of peptidoglycans is central to innate immunity,” he said.  “This shows that bacteria do a similar thing, but for different reasons.”  His team is anxious to understand the details better to make the comparison to the immune system as “there may be deep similarities.”

In addition to the promise for a new type of antibiotic medication, the news may stand to benefit the food industry.

Bacterial spores are also a significant problem for food preservation, Dworkin said, because they can withstand heat sterilization.  “If the food industry could find ways to control spore germination, that may be just as good as killing them,” he said.

The research, published in the October issue of the prestigious international journal Science, details how a huge molecule called a stressosome protects bacterial cells from external stress and danger.

Scientists from the University of Newcastle in Australia, and Newcastle University and Imperial College in the United Kingdom, collaborated on the discovery.

Associate Professor Peter Lewis from the Faculty of Science and Information Technology at the University of Newcastle in Australia said until now, researchers had not fully understood how bacteria responded to stress and potential danger.

“It is important to understand the changes that occur when bacteria are under stress as this is the point at which they are likely to become most infectious.

“The protein molecules that make up the stressosome are found in a very wide range of bacteria.  Some of these bacteria cause diseases such as listeriosis that has a 30 per cent mortality rate, and melioidosis that has a mortality rate as high as 90 per cent and is a significant health problem in northern Australia and south-east Asia.

“With bacteria becoming increasingly resistant to antibiotics, understanding how the stress response is controlled could lead to the development of drugs that help prevent bacterial infection from occurring.”

Lead author of the Science paper, Professor Rick Lewis from Newcastle University in the United Kingdom, said the team used groundbreaking techniques to observe the stressosomes.  Electron microscopy techniques were developed by Professor Marin van Heel of Imperial College and Associate Professor Peter Lewis developed the fluorescence microscopy imaging techniques.

“We knew that when bacteria were stressed, a warning signal would be sent from the surface to the inside of the cell.  The stressosome would then respond by triggering new proteins in the cell to react to the stress.

“Our latest work has revealed the structure and number of stressosomes per cell.  This has helped us understand how quickly the stressosomes respond to external stresses and prepare the cell to adapt to changes in its environment and ensure its survival.”

There is no evidence probiotics can relieve the symptoms of eczema, but there is some evidence that they may occasionally cause infections and gut problems.  These findings from The Cochrane Library come at a time when use of probiotics to treat eczema is increasing.

Eczema is an itchy skin condition that affects more than 1 in 20 people at some time in their lives and is especially common in children.  Its cause is complex and not well understood, but sufferers do have different bacteria in their guts compared to unaffected people.  Consequently, some nutritionists have suggested that eating live gut-dwelling bacteria, such as those found in probiotic yoghurts and some infant formulas, could be beneficial.

“Some doctors are recommending probiotics as a cheap treatment for eczema, but having carried out a systematic review we have found no evidence that they work for treating eczema,” says lead researcher Robert Boyle of Imperial College, London, UK.

The Cochrane Researchers looked at 12 studies that together involved 781 children diagnosed with eczema.  These studies compared severity of the disease in children given live bacteria to severity in those given a placebo.  The researchers found that probiotics provided no significant health improvement.  Similar bacteria were given across all studies, so the researchers could not rule out the possibility that other strains might be beneficial.  Moreover they found that in separate studies 46 patients had been reported to suffer side effects from using probiotics, including infection and bowel damage.

“There is no evidence that probiotics are a worthwhile treatment for eczema, and they may be harmful for certain groups of people,” says Boyle.  “However, further studies of new probiotics are needed, because it is possible that different types of probiotics which haven’t yet been studied in eczema treatment could be more effective.”

Chemicals used in the environment to kill bacteria could be making them stronger, according to a paper published in the October issue of the journal Microbiology.  Low levels of these chemicals, called biocides, can make the potentially lethal bacterium Staphylococcus aureus remove toxic chemicals from the cell even more efficiently, potentially making it resistant to being killed by some antibiotics.

Biocides are used in disinfectants and antiseptics to kill microbes.  They are commonly used in cleaning hospitals and home environments, sterilizing medical equipment and decontaminating skin before surgery.  At the correct strength, biocides kill bacteria and other microbes.  However, if lower levels are used the bacteria can survive and become resistant to treatment.

“Bacteria like Staphylococcus aureus make proteins that pump many different toxic chemicals out of the cell to interfere with their antibacterial effects,” said Dr Glenn Kaatz from the Department of Veterans Affairs Medical Center in Detroit, USA.  “These efflux pumps can remove antibiotics from the cell and have been shown to make bacteria resistant to those drugs.  We wanted to find out if exposure to biocides could also make bacteria resistant to being killed by the action of efflux pumps.”

The researchers exposed S. aureus taken from the blood of patients to low concentrations of several biocides and dyes, which are also used frequently in hospitals.  They looked at the effect of exposure on the bacteria and found that mutants that make more efflux pumps than normal were produced.

“We found that exposure to low concentrations of a variety of biocides and dyes resulted in the appearance of resistant mutants,” said Dr Kaatz.  “The number of efflux pumps in the bacteria increased.  Because the efflux pumps can also rid the cell of some antibiotics, pathogenic bacteria with more pumps are a threat to patients as they could be more resistant to treatment.”

If bacteria that live in protected environments are exposed to biocides repeatedly, for example during cleaning, they can build up resistance to disinfectants and antibiotics.  Such bacteria have been shown to contribute to hospital-acquired infections.

“Scientists are trying to develop inhibitors of efflux pumps.  Effective inhibitors would reduce the likelihood of additional resistance mechanisms emerging in bacteria,” said Dr Kaatz.  “Unfortunately, inhibitors evaluated to date do not work on a wide range of pathogens so they are not ideal to prevent resistance.”

“Careful use of antibiotics and the use of biocides that are not known to be recognised by efflux pumps may reduce the frequency at which resistant strains are found,” said Dr Kaatz.  “Alternatively, the combination of a pump inhibitor with an antimicrobial agent or biocide will reduce the emergence of such strains and their clinical impact.”

A bacteria cell’s ‘crisis command centre’ has been observed for the first time swinging into action to protect the cell from external stress and danger, according to new research out today (3 October) in Science.

The research team behind today’s study says that finding out exactly how bacteria respond and adapt to stresses and dangers is important because it will further their understanding of the basic survival mechanisms of some of the most resilient, hardy organisms on Earth.

The crisis command centre in certain bacteria cells is a large molecule, dubbed a ’stressosome’ by the scientists behind today’s research.  These cells have around 20 stressosomes floating around inside them, and although scientists knew they played an important role in the cell’s response to stressful situations, the complexities of this process had not been fully understood until now.

If a bacteria cell finds itself in a dangerous situation for example, if the temperature or saltiness of the bacteria’s environment reach dangerous levels which threaten the survival of the bacteria -a warning signal from the cell’s surface is transmitted into the cell.

Using cutting edge electron microscopy imaging techniques the authors of the new research observed that the stressosomes receive this warning signal, and in response several proteins called RSBT break away from the large stressosome.  This breakaway triggers a cascade of signals within the cell which results in over 150 proteins being produced proteins which enable the cell to adapt, react and survive in its new environment.

Professor Marin van Heel from Imperial College London’s Department of Life Sciences, one of the corresponding authors of the study, explains: “The cascade of events inside bacteria cells that occurs as a result of stressosomes receiving warning signals leads to particular genes inside the cell being transcribed more.  This means that some genes already active inside the cell are ‘turned up’ so that levels of particular proteins in the cell increase.  These changes to the protein make-up of the cell enable it to survive in a hostile or challenging environment.”

Dr Jon Marles-Wright from Newcastle University says: “Our work shows that cells respond to signals much like a dimmer on a light switch.  Now we’ll be building on this to work out how nature controls that dimmer switch.  We wouldn’t have been able to carry out this work without access to the Diamond synchrotron Light Source which has enabled us to examine the structures of individual stressosome proteins at atomic resolution.”

Dr Tim Grant, one of Imperial’s post doctoral researchers, adds that the key to bacteria cells’ success at surviving in rapidly changing environments is their speedy response: “The cell’s stressosomes are very good at their job as crisis command centres because they provide a very fast effective response to danger.  The chain reaction they kickstart produces results really quickly which enables bacteria to adapt to changes in their surroundings almost instantaneously.”

The team is now planning to collect very high resolution data of the stressosome complex on the world’s newest high-resolution cryo electron microscope, the FEI “KRIOS” that has just been installed in the Max Planck Institute in Martinsried, Germany.  Improving the resolution of the stressosome structure by a factor of two will lead to a resolution range normally only attainable by X-ray crystallography and will allow the researchers to directly see the amino-acid components of this fascinating complex.

As the southern pine beetle moves through the forest boring tunnels inside the bark of trees, it brings with it both a helper and a competitor.  The helper is a fungus that the insect plants inside the tunnels as food for its young.  But also riding along is a tiny, hitchhiking mite, which likewise carries a fungus for feeding its own larvae.

Now the picture of this peculiar, millennia-old arrangement has grown even more curious.  Writing in the Oct. 3 issue of Science, a team of researchers reports that the pine beetle harnesses a second microorganism – a bacterium known as an actinomycete – to protect its fungus from the mite’s competing one.  What’s more, the bacterium does so by wielding an antibiotic that is brand new to science.

The isolation of the novel antifungal compound – dubbed mycangimycin for the specialized compartments, or mycangia, in which the beetles carry both their fungi and bacteria – raises the intriguing possibility that other such discoveries could follow.

“There are perhaps 10 million species of insects on the planet,” says University of Wisconsin-Madison evolutionary biologist and symbiosis expert, Cameron Currie, who led the study with Harvard University chemist Jon Clardy.  “So, if insects associate with actinomycetes like this more generally, then there’s potentially a huge number of new places to explore.”

The realization couldn’t come at a better time.  Historically, the greatest source of antibiotics in the world has been the actinomycetes, especially members of the genus Streptomyces.  But in recent years, the number of new compounds successfully isolated from these organisms – and indeed from all microbes – has dwindled, even as resistance to existing antibiotics has spread.

Whether symbiotic associations end up being a treasure trove of new antimicrobials and other useful agents remains to be seen.  But it’s promising to see insects pairing up with actinomycetes.

“Actinomycetes are likely very attractive in these situations because of their potent antibiotic-producing abilities,” says UW-Madison graduate student, Jarrod Scott, who works with Currie.  “In much the same way that we recognize the power of these microorganisms, I think other organisms, in an evolutionary sense, have also recognized their power.”

Currie also has good reason to suspect these interactions are widespread.  In the 1990s, he was the first to discover that a fungus-farming ant, the leaf-cutter, used an actinomycete to protect its fungal crop from a parasitic mold.  That got him thinking about the importance of parasites and disease in the evolution of all organisms, and how these pressures may have led many insects to team up with beneficial microbes as a defense.

Beyond the leaf-cutting ants and pine beetles, one other example of this type of relationship is now established.  “But it hasn’t been systematically examined,” says Currie.  “If we actually start to look, we may find these associations to be very common.”

That one of the pine’s most devastating enemies in the southern United States and Mexico relies so heavily on a bacterium seems incredible, but that’s precisely the case for the southern pine beetle.  If the beetle’s fungus, Entomocorticium, is outgrown by the mite’s fungal partner, Ophiostoma, the beetle larvae will starve.  Holding Ophiostoma in check has therefore become the job of the actinomycete.

What’s interesting about the small molecule antibiotic it produces, though, is that it doesn’t seem to target Ophiostoma specifically.  The researchers instead suspect Entomocorticium has developed some resistance over time, says Scott, allowing it to survive the same low doses of antibiotic that wipe out its competitor.

This suggests the antibiotic could have broad-spectrum activity against other fungi and parasites, a possibility the team is now investigating.  And the discovery of a novel antifungal compound is especially exciting because many of these agents can serve double-duty as anticancer drugs, says Currie.

But for him and Scott, the greatest outcome would be wider recognition of the crucial role microbes play in the lives of all plants and animals, not just as parasites, but frequently as partners.

“Organisms like the pine beetle wouldn’t be able to do what they do without microbes,” says Scott.  “So, we’re interested in microorganisms as the basis of their success.

Researchers from Harvard Medical School and the University of Madison-Wisconsin have discovered how beetles and bacteria form a symbiotic and mutualistic relationship—one that ultimately results in the destruction of pine forests.  In addition, they’ve identified the specific molecule that drives this whole phenomenon.

The context of this discovery can easily be imagined as a story arc that includes some of the most unlikely characters and props.

Setting: The interior of a pine tree.

Enter the protagonist: The pine beetle, boring its way through the bark, a five millimeter arthropod ready to go into labor and lay a few hundred eggs.  Tucked in a specialized storage compartment in its shell, the beetle has a ready supply of spores for Entomocorticium, a nourishing fungal baby food for the beetle’s gestating larvae.

Enter the antagonist: The mite, a microscopic interloper that secretly hitched a ride on the beetle.

Conflict: Unbeknownst to mother pine beetle, the mite has snuck in a supply of Ophiostoma minus, a pathogenic fungi that can wipe out the entire supply of fungal larvae food.  The mite releases this toxin.

Climax: Will the baby beetles die of starvation?

Resolution: Catching the mite off guard—as well as the scientists conducting the study!—the mother beetle is ready with actinomycetes, a bacteria that neutralizes the toxic fungi by means of a tiny fatty acid.

Conclusion: While actinomycetes rescues the baby beetles from certain starvation, the larvae-friendly Entomocorticium softens up the pine, allowing the fledgling beetles to eat not only the fungi but the tree itself.  Soon, the young beetles leave to begin their new lives.  Mother beetle gathers up the remaining supply of Entomocorticium and heads for another tree.  The beetles live, and the infernal mite is thwarted.

Surprise ending: The camera pans back, and we quickly realize that the beetles’ success has cost the tree its life.  An aerial view reveals miles and miles of dead pine forest, and, as the ominous audio track implies, scores of pine beetles will continue moving from tree to tree leaving ravished forests in their wake.

“So you have a beetle, a mite, a tree, two kinds of fungi, and a bacterium,” says Jon Clardy, Harvard Medical School professor of biological chemistry and molecular pharmacology who, along with Cameron Currie from the University of Madison-Wisconsin, is co-senior author on the study.  “Discovering this particular bacterium, and the active molecule, has added the molecular dimension to this chemical ecology of this complex multi-lateral system.  It highlights the importance of bacteria in ways that people don’t really even think about.”

The findings will be published in the October 3 issue of Science.

The ground work for this study began in 1999 when Currie published a paper demonstrating how leafcutter ants mediate their fungal environment through bacteria.  Suspecting that this phenomenon may be common throughout the animal kingdom, Currie teamed up with Clardy to examine the pine beetle.

Pine beetles are like little landscape engineers, drilling through the bark and into pine trees, using fungus to create an environment in which to lay their eggs.  As a result of this activity, thousands of miles of trees are destroyed each year, often resulting in widespread forest fires.  Regions such as western Canada are particularly affected by this.

Experts have known that just like the fungus-growing ants, pine beetles also use fungus to feed their larvae, and that they often managed to avoid the adverse affects of pathogenic fungi often present in the tree.  But the precise means by which they interact with fungal microbes has never been demonstrated.

Currie and research assistant Jarrod Scott discovered that the beetle carries a bacteria in a specialized compartment, and after a series of experiments found that the bacteria produced an antifungal agent that killed the pathogenic fungi snuck in by the trespassing mite.

In order to delve deeper into how the bacteria works, Dong-Chan Oh, a postdoctoral researcher in Clardy’s Harvard Medical School lab, used a variety of laboratory tools, such as nuclear magnetic resonance techniques and chromatography, to both locate the molecule and identify its structure.  The molecule turns out to be a kind of fatty acid.

“It’s becoming clear that symbiotic relationships between plants, animals, and microbes are essential for the diversification of life and evolution of organisms,” says Currie.  “This is an example of a system where we have insights into the importance of the diversity of microbes.  We believe that this type of mutualism is widespread.”

In addition, the researchers suspect that this association represents a source of small molecules that can be used in medicine.

“This molecule is nature’s anti-fungal,” says Clardy, “and it looks like there are a lot of them.”

This is particularly significant, since pathogenic fungal infections in people are a major health concern.  These infections are often fatal, and at the moment, no reliable medications for them exist.  Here, however, we have an example of an antibiotic successfully disabling a powerful fungi.

“This particular molecule is too unstable to be a viable candidate,” says Clardy.  “Still, we need to study how it kills fungi, learn the mechanisms.  We can look into other bacterial genomes and investigate other anti-fungal processes.”

Suspecting that this symbiotic dynamic is far more the rule than the exception, Clardy and Currie are investigating other insect species as well to see how universal this “story arc” is.

Oliver Söhnlein and colleagues, at the Karolinska Institutet, Sweden, have identified a new function for a number of proteins secreted by human immune cells known as neutrophils or PMNs: they enhance the uptake of bacteria by other immune cells (known as macrophages) that are capable of destroying the microbes.

In the study, proteins secreted by human PMNs, specifically HBP and HNP1-3, were found to enhance the in vitro ability of human and mouse macrophages to take up bacteria coated in the immune molecule IgG. Mechanistically, HBP and HNP1-3 activated the macrophages to secrete soluble factors that, in turn, induced the macrophages to express proteins to which IgG can bind (CD32 and CD64). The authors therefore suggest that HBP and HNP1–3 secreted by PMNs have a role in clearing bacterial infections.

Yeast, the essential microorganism for fermentation in the brewing of beer, converts carbohydrates into alcohol and other products that influence appearance, aroma, and taste.  In a study published online today in Genome Research, researchers have identified the genomic origins of the lager yeast Saccharomyces pastorianus, which could help brewers to better control the brewing process.

For thousands of years, ale-type beers have been brewed with Saccharomyces cerevisiae (brewer’s or baker’s yeast).  In contrast, lager beer, which utilizes fermentations carried out at much lower temperature than for ale, is a more recently developed alcoholic beverage, appearing in Bavaria near the end of the Middle Ages.  Lager beer gained worldwide popularity starting in the late 1800s, when the advent of refrigeration made year-round low-temperature fermentations possible.  Saccharomyces pastorianus, the yeast used in lager brewing, is a “hybrid” organism of two yeast species, Saccharomyces bayanus and S. cerevisiae.  It is thought that the contributions of both parent species resulted in an organism able to out-compete other yeasts during the cold lager fermentations.

Though early brewers understood that different brewing conditions would produce a unique beer, scientists are now unlocking the genetic differences between yeast strains that produce variation in flavor, color, and aroma.  By comparing the genomic properties of yeast strains sampled from breweries around the world, Drs.  Barbara Dunn and Gavin Sherlock of Stanford University have measured the genetic contribution of the parent yeasts to strains of S. pastorianus and revealed new insights into the events that brought about the evolution of lager yeast.

Surprisingly, the researchers found evidence that S. pastorianus strains used by brewers today may not have arisen from a single hybridization event, as was previously believed.  “There were two independent origins of today’s extant S. pastorianus strains,” said Sherlock.  “It is likely that each of these groups derived the S. cerevisiae portions of their genomes from distinct but related ale yeasts, and that these natural hybrids were then selected by brewers due to their abilities to ferment at cold temperatures.”

While this work identified two distinct groups of S. pastorianus, Sherlock noted that they observed significant genetic variation and flexibility within the groups as well.  Dunn and Sherlock speculated this genomic flexibility could have implications for the unique properties of each brewer’s beer.  “The fact that lager yeasts isolated from different breweries each seem to have a unique genomic make-up may indicate that the yeasts are adapting to the conditions specific to each brewery,” explained Dunn.

Furthermore, this work paves the way for the characterization of specific genetic features of each strain that could aid in the brewing process.  “Our discovery that unique genomic structures may be characteristic to each brewery and/or beer type could lead to insights on how to directly control flavor and aroma in beer,” said Dunn.

Heart disease is the leading cause of death worldwide.  However, many people with cardiovascular disease have none of the common risk factors such as smoking, obesity and high cholesterol.  Now, researchers have discovered a new link between gum disease and heart disease that may help find ways to save lives, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

In recent years chronic infections have been associated with a disease that causes “furring” of the arteries, called atherosclerosis, which is the main cause of heart attacks.  Gum disease is one of the most common infections of humans and there are now over 50 studies linking gum disease with heart disease and stroke.

“A number of theories have been put forward to explain the link between oral infection and heart disease,” said Professor Greg Seymour from the University of Otago Dunedin, New Zealand.  “One of these is that certain proteins from bacteria initiate atherosclerosis and help it progress.  We wanted to see if this is the case, so we looked at the role of heat shock proteins.”

Heat shock proteins are produced by bacteria as well as animals and plants.  They are produced after cells are exposed to different kinds of stress conditions, such as inflammation, toxins, starvation and oxygen and water deprivation.  Because of this, heat shock proteins are also referred to as stress proteins.  They can work as chaperone molecules, stabilising other proteins, helping to fold them and transport them across cell membranes.  Some also bind to foreign antigens and present them to immune cells.

Because heat shock proteins are produced by humans as well as bacteria, the immune system may not be able to differentiate between those from the body and those from invading pathogens.  This can lead the immune system to launch an attack on its own proteins.  “When this happens, white blood cells can build up in the tissues of the arteries, causing atherosclerosis,” said Professor Seymour.

“We found white blood cells called T cells in the lesions of arteries in patients affected by atherosclerosis.  These T cells were able to bind to host heat shock proteins as well as those from bacteria that cause gum disease.  This suggests that the similarity between the proteins could be the link between oral infection and atherosclerosis,” said Professor Seymour.

This molecular mimicry means that when the immune system reacts to oral infection, it also attacks host proteins, causing arterial disease.  These findings could fundamentally change health policy, highlighting the importance of adult oral health to overall health and wellbeing: control of gum disease should be essential in reducing the risk of heart disease.

“This is a significant step towards a more complete understanding of heart disease and improving treatment and preventive therapies,” said Professor Seymour.  “An understanding of all the possible risk factors could help lower the risk of developing heart disease and lead to a significant change in disease burden.”

Bacteria found in compost heaps able to convert waste plant fibre into ethanol could eventually provide up 10% of the UK’s transport fuel needs, scientists heard today (Tuesday 9 September 2008) at the Society for General Microbiology’s Autumn meeting being held this week at Trinity College, Dublin.

Researchers from Guildford, UK, have successfully developed a new strain of bacteria that can break down straw and agricultural plant waste, domestic hedge clippings, garden trimmings and cardboard, wood chippings and other municipal rubbish to convert them all into useful renewable fuels for the transport industry.

“The bioethanol produced in our process can be blended with existing gasoline to reduce overall greenhouse gas emissions, help tackle global warming, reduce dependence upon foreign oil and help meet national and international targets for renewable energy,” said Paul Milner, Fermentation Development Manager of TMO Renewables Ltd, based in Surrey Research Park, Guildford.

The new strain of bacteria allows ethanol to be produced much more efficiently and cheaply than in traditional yeast-based fermentation, which is based on the beer-brewing process and forms the basis for most current commercial bioethanol production.

“Conventional ethanol production is energy-intensive, expensive, and time-consuming as the barley malt or other material being brewed needs to be heated up as a mash in feedstock pre-treatment.  Then it is significantly cooled from that high temperature to a lower temperature for yeast fermentation, only to be re-heated when it is later distilled into ethanol.  Our process is much more energy-efficient.”  Said Paul Milner.

TMO’s microbiologists screened thousands of different wild types of bacteria, looking for one that could survive high temperatures and that liked feeding off a wide variety of plant based materials.

“We found some heat-loving bacteria in a compost heap, from the Geobacillus family, which in their wild form produce lactic acid as a by-product of sugar synthesis when they break down biomass,” said Paul Milner.  “We altered their internal metabolism, adapting them to produce substantial amounts of ethanol instead”.

“Our new microorganism, called TM242, can efficiently convert the longer-chain sugars from woody biomass materials into ethanol.  This thermophilic bacterium operates at high temperatures of 60oC-70oC and digests a wide range of feedstocks very rapidly,” said Paul Milner.

The scientists estimate that some 7 million tons of surplus straw is available in the UK every year.  Turning it into ethanol could replace 10% of the gasoline fuel used in this country.  “As our process uses agricultural waste materials such as straw, wood, paper and plants and other cellulosic fibre from domestic and municipal waste, it provides significantly greater environmental and economic benefits than crop-derived biofuels which some believe have contributed to the increased prices of basic food in so many countries,” said Paul Milner.

“We have recently completed commissioning the UK’s first cellulosic ethanol demonstration facility – one of just a handful worldwide,” said Paul Milner.  “We are constantly researching new, better ways to produce biofuels.  We also believe that our process can be used successfully beyond biofuels to produce other high-value chemicals and drug ingredients that are currently derived from oil.”

Substances in marijuana show promise for fighting deadly drug-resistant bacterial infections, including so-called “superbugs,” without causing the drug’s mood-altering effects, scientists in Italy and the United Kingdom are reporting.  Besides serving as infection-fighting drugs, the substances also could provide a more environmentally-friendly alternative to synthetic antibacterial substances now widely used in personal care items, including soaps and cosmetics, they say.  Their study is scheduled for the Sept. 26 issue of ACS’ monthly Journal of Natural Products.

In the new study, Giovanni Appendino and colleagues point out that scientists have known for years that marijuana contains antibacterial substances.  However, little research has been done on those ingredients, including studies on their ability to fight antibiotic resistant infections, the scientists say.

To close that gap, researchers tested five major marijuana ingredients termed cannabinoids on different strains of methicillin-resistant Staphylococcus aureus (MRSA), a “superbug” increasingly resistant to antibiotics.  All five substances showed potent germ-killing activity against these drug-resistant strains, as did some synthetic non-natural cannabinoids, they say.  The scientists also showed that these substances appear to kill bacteria by different mechanisms than conventional antibiotics, making them more likely to avoid bacterial resistance, the scientists note.  At least two of the substances have no known mood-altering effects, suggesting that they could be developed into marijuana-based drugs without causing a “high.”

A small molecule that locks an essential enzyme in an inactive form could one day form the basis of a new class of unbeatable, species-specific antibiotics, according to researchers at Fox Chase Cancer Center.

Their findings, highlighted on the cover of the June 23 issue of the journal Chemistry & Biology, take advantage of an emerging body of science regarding “morpheeins” – proteins made from individual components that are capable of spontaneously reconfiguring themselves into different shapes within living cells.

The researchers discovered a small molecule, which they have named morphlock-1, binds the inactive form of a protein known as porphobilinogen synthase (PBGS), an enzyme used by nearly all forms of cellular life.  The functioning form of PBGS is built from eight identical component parts – in what is called an octamer configuration – and is essential among nearly all forms of life in the processes that enable cells to use energy.  The other configuration is made of six parts – or a hexamer configuration – and serves as a “standby” mode for the protein.

“As the name suggests, morphlock-1 essentially locks the hexamer configuration into place, preventing its protein subunits from reconfiguring into the active assembly,” says lead investigator Eileen Jaffe, Ph.D, a Senior Member of Fox Chase.  “Targeting morpheeins in their inactive assemblies provides an entirely new approach to drug discovery.”

While their study was performed using a pea plant-version of PBGS, the researchers have reason to believe the principle could apply to bacterial versions of PBGS as well.  “Using morphlock-1 as a base, we are seeking to fine tune the molecule so that it blocks just the bacterial version of the PBGS enzyme, ” Jaffe says.

“Because PBGS is so crucial for life, the part of the enzyme where chemistry happens is highly conserved through evolution,” Jaffe says, meaning that an all-around PBGS-inhibiting drug would harm bacteria, peas and people alike.  The area where the potential drug binds to the hexamer form of the protein, however, has been found to differ among species, depending how far the organisms have evolved from each other.

When PBGS is in its inactive hexamer form, there is a small cavity on the surface of the assembled complex.  Using computer docking techniques, Jaffe and her Fox Chase colleagues identified a suite of small molecules predicted to bind to this cavity.

The researchers then bought and tested a selection of these molecules in the lab to see if any of them stabilized the pea PBGS in its hexamer assembly.  One inhibitor in particular, given the name morphlock-1, potently drove the formation of the hexamer in pea PBGS, but not in that of humans, fruit flies, or the infectious bacteria Pseudomonas aeruginosa, or Vibrio cholerae, the latter of which causes cholera.  Morphlock-1 is a potent inhibitor of pea PBGS, but not of the PBGS from these other organisms.

Jaffe coined the term “morpheein” in 2005 after a study of the structure of PBGS revealed its shape-shifting tendencies.  While initially met with skepticism because the existence of morpheeins contradicts some classic concepts about protein structure and function, subsequent studies have reinforced that PBGS (and perhaps other proteins) exhibits this behavior.  According to Jaffe, this study is the first to make use of alternate morpheein shapes as a potential strategy for drug discovery, in general, particularly for antibiotics.

“Multi-drug resistance drives the need for developing new antibiotics,” Jaffe says.  “Since drugs that stabilize the inactive PBGS hexamer need not be chemically similar to each other, it will be difficult for the bacterium to develop complete resistance to a cocktail of such compounds.”

A tiny but powerful engine that propels the bacterium Bacillus subtilis through liquids is disengaged from the corkscrew-like flagellum by a protein clutch, Indiana University Bloomington and Harvard University scientists have learned. Their report appears in this week’s Science.Scientists have long known what drives the flagellum to spin, but what causes the flagellum to stop spinning — temporarily or permanently — was unknown.

“We think it’s pretty cool that evolving bacteria and human engineers arrived at a similar solution to the same problem,” said IU Bloomington biologist Daniel Kearns, who led the project. “How do you temporarily stop a motor once it gets going?”

The action of the protein they discovered, EpsE, is very similar to that of a car clutch. In cars, the clutch controls whether a car’s engine is connected to the parts that spin its wheels. With the engine and gears disengaged from each other, the car may continue to move, but only because of its prior momentum; the wheels are no longer powered.

EpsE is thought to “sit down,” as Kearns describes it, on the flagellum’s rotor, a donut-shaped structure at the base of the flagellum. EpsE’s interaction with a rotor protein called FliG causes a shape change in the rotor that disengages it from the flagellum’s proton-powered engine.

The discovery of EpsE and its function was accidental. Kearns and colleagues were actually interested in learning more about the genes that cause individual cells of B. subtilis to cease wandering in solitude and take up residence in a massively communal, stationary assemblage called a biofilm. The stability of biofilms can be jeopardized by hyperactive bacterial cells whose flagella continue to spin.

“We were trying to get at how the bacterium’s ability to move and biofilm formation are balanced,” Kearns said. “We were looking for the genes that affected whether the cells are mobile or stationary. Although B. subtilis is harmless, biofilms are often associated with infections by pathogenic bacteria. Understanding biofilm formation may eventually prove useful in combating bacterial infections.”

Once the scientists learned EpsE was involved in repressing flagellar motion, they devised two possible explanations for how EpsE acts. The first was that EpsE acts like a brake by pushing a non-moving part against a moving part and locking up the works. The other possibility, they imagined, was that EpsE acts like a clutch, disengaging one moving part from another. In this latter scenario, the engine can no longer drive flagellar spinning because key moving parts are no longer in contact. In this case, the flagellum would still have freedom of motion, listless as it might be.

To determine which hypothesis was correct, the scientists decided it best to let the tail wag the dog. They attached the tail end of the flagellum to a glass slide and examined the movement of the entire cell in the presence and absence of EpsE. In the absence of EpsE, the entire cell rotated once every five seconds. In the presence of EpsE, the cells stopped but could rotate passively, pushed by disturbances in the environment (Brownian motion). If EpsE acted like a brake, the cells would not have rotated at all.

The researchers also learned that when the cell begins producing EpsE, it takes about 15 minutes before the flagellar machinery is disabled.

“This makes a lot of sense as far as the cell is concerned,” Kearns said. “The flagellum is a giant, very expensive structure. Often when a cell no longer needs something, it might destroy it and recycle the parts. But here, because the flagellum is so big and complex, doing that is not very cost effective. We think the clutch prevents the flagellum from rotating when constrained by the sticky matrix of the biofilm.”

The discovery may give nanotechnologists ideas about how to regulate tiny engines of their own creation. The flagellum is one of nature’s smallest and most powerful motors — ones like those produced by B. subtilis can rotate more than 200 times per second, driven by 1,400 piconewton-nanometers of torque. That’s quite a bit of (miniature) horsepower for a machine whose width stretches only a few dozen nanometers.