When good gut bacteria get sick

Being sick due to an infection can make us feel lousy. But what must the ecosystem of bacteria, or microbiota, colonizing our guts be going through when hit with infection? A study from Brigham and Women's Hospital (BWH) has utilized unique computational models to show how infection can affect bacteria that naturally live in our intestines. The findings may ultimately help clinicians to better treat and prevent gastrointestinal infection and inflammation through a better understanding of the major alterations that occur when foreign bacteria disrupt the gut microbiota.

"Our gut contains ten-times more bacterial cells than there are human cells in our body," said Lynn Bry, MD, PhD, director of the BWH Center for Clinical and Translational Metagenomics, senior study author. "The behavior of these complex bacterial ecosystems when under attack by infection can have a big impact on our health."

The study is published July 11, 2014 in PLOS ONE.

Georg Gerber, MD, PhD, MPH, co-director of the BWH Center for Clinical and Translational Metagenomics, co-first study author, developed novel computer algorithms to analyze the different stages of infection when a pathogen known as Citrobacter rodentium, which causes disease in mice similar to food-poisoning in humans, was introduced into the guts of mice. Bry and her team generated a two-month time-series of the population levels of bacteria throughout multiple sites in the intestine. The computational framework, known as Microbial Counts Trajectories Infinite Mixture Model Engine, developed by Gerber, was used to identify dynamic changes within the complex communities of bacteria in the gut associated with infection and inflammation.

The researchers observed many disruptions in the normal bacteria at different locations in the gut during the infection. For instance, they discovered a microbial signature in the colon involving species belonging to the genus Mucispirillum that showed decreases early in infection before the onset of symptoms. Other signatures included increases in populations of bacteria from the Clostridiales and Lactobacillales families occurring after the pathogen had disappeared. Interestingly, some of these signatures occurred in locations in the gut where the pathogen was not directly damaging host cells.

"From a clinical perspective, these new microbial signatures we identified could help clinicians detect early stages of inflammation or subtle persistent disease in patients with gastrointestinal disorders, such as inflammatory bowel disease," said Bry. "Moreover, several time-dependent microbial signatures we identified may be leveraged to conduct further research of other infectious and inflammatory conditions."

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The above story is based on materials provided by Brigham and Women's Hospital . The original article was written by Marjorie Montemayor-Quellenberg. Note: Materials may be edited for content and length.

Beloved crape myrtle in nurseries now susceptible to bacterial leaf spot

It's enough to send gardeners into conniptions.

Crape myrtle, a tree adored for its bright flowers that scream summer, care-free maintenance and even its colorful bark, now has a disease problem -- although so far, only in the commercial nursery setting.

University of Florida researchers had been getting sporadic reports from nursery owners over the last five years of a leaf spot problem, and those reports have only increased in frequency. Through genetic testing, scientists identified the disorder as being caused by the bacterium Xanthomonas axonopodis. The disease is most likely spread by wind-driven rain or overhead irrigation, and some crape myrtle varieties are more susceptible than others.

"I've been working with crape myrtles for a long time, and they've been such a disease-resistant plant for such a long time, so it's pretty significant when their susceptibility to disease is increased," said Gary Knox, an environmental horticulture professor with UF's Institute of Food and Agricultural Sciences.

The U.S. crape myrtle crop had a value of nearly $43 million in 2010, and Florida is its second-biggest producer, behind Texas. Florida has more companies producing crape myrtle, however, with 130 compared with 72 in Texas.

In the June issue of the journal Plant Disease, the UF/IFAS team outlined the first report of the disease and the work they did to identify it. They believe it is the first report of the bacterium causing leaf spot in crape myrtle.

Bacterial leaf spot doesn't kill the ornamental tree, but creates spots on its leaves that eventually turn yellow and drop.

The researchers say, for now, the disease affects only crape myrtle commercial producers and is spread by factors such as overhead irrigation systems and large numbers of plants kept in close quarters.

The bad news is that the bacterium is widespread.

"I think you can safely say that nearly every crape myrtle producer would have the disease at this point," Knox said.

While the disease appears contained in the commercial sector, that could change.

"Most bacterial diseases can be spread in wind-driven rain, and in Florida, we know there's no shortage of that," said Mathews Paret, an assistant professor of plant pathology who led the study.

Paret and Knox are based at the North Florida Research and Education Center in Quincy.

Scientists suggest an integrated management approach to the problem, rather than a silver bullet that only stops the problem temporarily.

Choosing resistant varieties, moving from overhead irrigation to drip irrigation and the limited use of bactericides would be part of such an integrated strategy, the researchers said.

The varieties Natchez, Osage, Fantasy, Basham's Party Pink and Miami have proven highly resistant to bacterial leaf spot while Carolina Beauty, Arapaho, Tuscarora, White Chocolate, Red Rocket and Rhapsody in Pink were more susceptible in field trials funded by the Florida Nursery Growers and Landscape Association.

Steve Bender, a senior writer at Southern Living magazine, "The Grumpy Gardener" blogger and well-known gardening author, says it would be a huge disappointment if the disease ever makes the leap from nurseries to home gardens.

Crape myrtle is so close to Southern gardeners' hearts that they endlessly debate such topics as how to spell its name (variants include crepe myrtle, crape myrtle and even crapemyrtle), and the annual rite Bender calls "crape murder" -- an unceremonious lopping of its limbs.

It's an iconic tree, he said, mostly because it's little work for a big payoff.

"It's ideally suited to the southern climate, it blooms for a long time, it comes in lots of different colors and you even get nice color in the fall," Bender said. "It's kind of hard to kill, and pretty much any idiot can grow one. And up until now, it's had very few problems."

Technology developed to redirect proteins towards specific areas of genome

The Spanish National Cancer Research Centre (CNIO) Macromolecular Crystallography Group has managed to reprogramme the binding of a protein called BuD to DNA in order to redirect it towards specific DNA regions. Guillermo Montoya, the researcher who led the study, says the discovery: "will allow us to modify and edit the instructions contained in the genome to treat genetic diseases or to develop genetically-modified organisms." The study is published in the journal Acta Crystallographica, Section D: Biological Crystallography.

The possibility of making à la carte modifications to the genome of living organisms could have a wide variety of applications, not only in the field of synthetic biology -- the science that seeks to create new living beings or improve existing ones for their biotechnological use -- but also for the treatment of human illnesses.

To achieve this, several researchers from around the world have focused on the proteins that bind to the DNA in very specific ways: their manipulation to direct them towards specific places in the genome, linked to their binding to genetic effectors (DNA repair or activator proteins, among others), could serve to modify DNA messages or to redesign genetic circuits as needed.

The CNIO team has deciphered the DNA binding code of BurrH, a new protein that was identified in Burkholderia rhizoxinica bacteria whose BuD domain specifically binds to the genome. To get there, the researchers have resolved the complete three-dimensional structure of the protein using the biophysical technique known as X-ray crystallography.

The main advantage of BuDs lies in their high specificity: they are able to distinguish DNA sequences that differ only in two nucleotides (the letters that make up the DNA). "This high specificity acts as a GPS that allows them to find their destinations within the intricate genome map," says Montoya, adding that: "They are very versatile and easy to reprogram in comparison with other proteins used to the same end."

Montoya's group has redesigned BuDs that are capable of recognizing the areas of the genome close to mutations responsible for sickle-cell disease, a pathology caused by modifications in the beta globin gene that produce alterations in red blood cells. "The linking of DNA repair proteins to these redesigned BuDs could serve to correct genetic alterations in patients with this disease," say the researchers.

Montoya says that several companies are already interested in this new technology: "Our tool, as well as being used to treat genetic disease, could be used to genetically modify micro-organisms targeting metabolite synthesis needed to produce biofuels, for example."

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The above story is based on materials provided by Centro Nacional de Investigaciones Oncologicas (CNIO) . Note: Materials may be edited for content and length.