A low-cost technology may make it possible to read long sequences of DNA far more quickly than current techniques.

The research advances a technology, called nanopore DNA sequencing. If perfected it could someday be used to create handheld devices capable of quickly identifying DNA sequences from tissue samples and the environment, the 91̽�� researchers who developed and tested the approach said.

“One reason why people are so excited about nanopore DNA sequencing is that the technology could possibly be used to create ‘tricorder’-like devices for detecting pathogens or diagnosing genetic disorders rapidly and on-the-spot,” said Andrew Laszlo, lead author and a graduate student in the laboratory of Jen Gundlach, a 91̽��professor of physics who led the project.

The paper “Decoding long nanopore sequencing reads of natural DNA”  describes the new technique. It appears June 25 in the advanced online edition of the journal Nature Biotechnology.

Most of the current gene sequencing technologies require working with short snippets of DNA, typically 50 to 100 nucleotides long. These must be processed by large sequencers in a laboratory. The cumbersome process can take days to weeks to complete.

Nanopore technology takes advantage of the small, tunnel-like structures found in bacterial membranes. In nature, such pores allow bacteria to control the flow of nutrients across their membranes.

91̽��researcher used the nanopore  (MspA). This bacterial pore has been genetically altered so that the narrowest part of the channel has a diameter of about a nanometer, or 1 billionth of a meter. This is large enough for a single strand of DNA to pass through. The modified nanopore is then inserted into a membrane separating two salt solutions to create a channel connecting the two solutions.

To read a sequence of DNA with this system, a small voltage is applied across the membrane to make the ions of the salt solution flow through the nanopore. The ion flow creates a measurable current. If a strand of DNA is added to the solution on one side of the membrane and then enters a pore, the bulky DNA molecules will impede the flow of the much smaller ion and thereby alter the current. How much the current changes depends on which nucleotides — the individual molecules adenine, guanine, cytosine and thymine that make up the DNA chain — are inside the pore. Detecting changes in current can reveal which nucleotides are passing through the nanopore’s channel at any given instant.

Since the technique was first proposed in the 1990s, researchers hoped that nanopore DNA sequencing would offer a cheap, fast alternative to current gene sequencing. But their attempts have been frustrated by several challenges. It is difficult to identify each nucleotide one-by-one as they pass through the nanopore. Instead, researchers have to work with changes in current associated with four nucleotides at a time. In addition, some nucleotides may be missed or read more than once. Consequently, current nanopore sequencing technology yields an imprecise readout of a DNA sequence.

The 91̽��researchers describe how they bypassed these problems. The researchers first identified the electronic signatures of all the nucleotide combinations possible with the four nucleotides that make up DNA — a total of 256 combinations in all (4 x 4 x 4 x 4).

They then created computer algorithms to match the current changes generated when a segment of DNA passes through the pore with current changes expected  from DNA sequences of known genes and genomes stored in a computer database. A match would show that the sequence of the DNA passing through the pore was identical or close to the DNA sequence stored in the database. The whole process would take minutes to a few hours, instead of weeks.

To test this approach, the researchers used their nanopore system to read the sequence of bacteriophage Phi X 174, a virus that infects bacteria and that is commonly used to evaluate new genome sequencing technologies. They found that the approach reliably read the bacteriophage’s DNA sequences and could  read sequences as long as 4,500 nucleotides.

“This is the first time anyone has shown that nanopores can be used to generate interpretable signatures corresponding to very long DNA sequences from real-world genomes,” said co-author Jay Shendure, a 91̽��associate professor of genome sciences whose lab develops applications of genome sequencing technologies.  “It’s a major step forward.”

Because the technique relies on matching readings to databases of previously sequenced genes and genomes, it cannot yet be used to sequence a newly discovered gene or genome, the researchers said, but with some  refinements, they added, it should  be possible to improve performance in this area. To accelerate research on this new technology, the scientists are making their methods, data and computer algorithms fully available to all.

“Despite the remaining hurdles, our demonstration that a low-cost device can reliably read the sequences of naturally occurring DNA and can interpret DNA segments as long as 4,500 nucleotides in length represents a major advance in nanopore DNA sequencing,” Gundlach said.

This work was supported by the National Institutes of Health, National Human Genome Research Institutes $1,000 Genome Program Grants R01HG005115, R01HG006321 and R01HG006283  and a graduate research fellowship from the National Science Foundation DGE-0718124.

Stem cell therapy can regenerate heart muscle in primates, according to a UW-led study. The scientists on this and related projects are seeking way to repair hearts weakened by myocardial infarctions. This all-too-common type of heart attack blocks a major artery and deprives heart muscle of oxygen.

People who survive a severe episode often continue their lives in poor health because their hearts no longer work properly. The researchers hope eventually to restore such failing hearts to normal function. Their approach uses heart cells created from human embryonic stem cells

The researchers tested the possibility of producing enough of these cardiac muscle cells to remuscularize damaged hearts in a large animal whose heart size and physiology are human-like.

Their results are reported today, April 30, in the advanced online edition of Nature. See .

Dr. Charles Murray, professor of pathology and bioengineering, and Dr. Michael LaFlamme, assistant professor of pathology, are the senior authors of the paper.

Read the details of their project and its outcomes in, and watch a video describing the research.

The study appears in this week’s issue of the New England Journal of Medicine. The lead author is Anna Wald, M.D., professor  of medicine, epidemiology, and laboratory medicine, and medical director at the Virology Research Clinic at the 91̽��. Other 91̽��coauthors include Dr. Amalia Magaret, Dr. Christine Johnston, Dr. Lawrence Corey, Dr. Meei-Li Huang and Stacy Selke.

“These data suggest this drug may be a potent treatment for HSV-2,” said Wald. “That’s exciting because we have not had a new drug for herpes for three decades. In addition, our approach of using viral shedding as an endpoint clearly defined the dose that should be used in future studies”

Roughly one in six Americans aged 14 to 49 years has genital herpes. Most recurrent genital herpes are caused by with herpes simplex virus 2 (HSV-2). The infection, which is usually transmitted through sexual contact, can cause pain and sores in the genital area, anal region and lips.

But in most cases symptoms can be mild or altogether absent. As a result, most people who have been infected with HSV-2 are unaware they are infected, though they can still transmit the virus to others.

Currently, there are treatments that shorten outbreaks, prevent recurrences and reduce transmission to sex partners, and but there is no cure.

These treatments include the prescription drugs Acyclovir (Zovirax), Valacyclovir (Valtrex) and Famciclovir (Famvir), which all inhibit viral replication by inhibiting a viral enzyme called HSV DNA polymerase.

The new drug, pritelivir, is the first in a new class of drugs that inhibit HSV by targeting a different part of the virus’s replication machinery, the helicase-primase enzyme complex.

In the new study, 156 patients with genital HSV-2 infection were randomized to receive either placebo or four different dosage regimens of the new drug for 28 days.

The four dosing regimens for pritelivir were: a loading dose of 20 mg followed by a daily dose of 5 mg; a loading dose of 100 mg followed by a daily dose of 25 mg; a loading dose of 300 mg followed by a daily dose of 75 mg; and a weekly dose of 400 mg.

All the patients kept a diary recording any signs and symptoms of the infection and swabbed their genital areas daily. The swabs were then tested to detect and quantify any shedding of the virus.

The 75 mg a day dosing schedule proved to be the most effective, the study found. That dose was associated with an 87 percent reduction in days of viral shedding, from 16.6 percent among those taking the placebo to 2.1 percent among those taking 75 mg of the drug a day. What’s more, substantially less virus was present during breakthrough shedding in persons receiving pritelivir, another indication of the drug’s efficacy.

The 75 mg treatment regimen was also associated with fewer days with genital lesions.  Compared to those on placebo, who reported genital lesions on 9.0 percent of days, those on pritelivir 75 mg a day reported lesions only 1.2 percent of days, an 87 percent reduction.

Side effects of the treatment were few and mild, and there were no signs of drug resistance developing. However, further clinical studies of the drug are on hold, while the U.S. Food and Drug investigates the findings of a toxicology study in which monkeys receiving high doses of pritelivir, doses 70 to 900 times as high as a 75 mg dose in humans, developed blood and skin abnormalities.

Read the New England Journal of Medicine paper:

Wald A et al. Helicase–Primase Inhibitor Pritelivir for HSV-2 Infection. N Engl J Med 2014;370:201-10. DOI: 10.1056/NEJMoa1301150

This phenomenon is crucial in the bacteria’s struggle for survival. The more diversity a population of bacteria has, the more likely it will contain individuals able to take advantage of a new opportunity or overcome a new threat, including the threat posed by an antibiotic.

In a recent study, researchers at the 91̽�� showed that when a bacterial cell divides into two daughter cells there can be an uneven distribution of cellular organelles. The resulting cells can behave differently from each other, depending on which parts they received in the split.

“This is another way that cells within a population can diversify. Here we’ve shown it in a bacterium, but it probably is true for all cells, including human cells,” said Dr. Samuel Miller, 91̽��professor of microbiology, genome sciences, and medicine and the paper’s senior author.

Bridget Kulasekara, who obtained a Ph.D in the 91̽��Molecular and Cellular Biology Program, was the paper’s lead author. Other contributors included: Hemantha Kulasekara, Matthias Christen, and Cassie Kamischke, who work in Miller’s lab, and Paul Wiggins, 91̽��assistant professor of physics and bioengineering. The paper appears in the online journal eLife.

In an earlier paper, Miller and his colleagues showed that when bacteria divided, the concentration of an important regulatory molecule, called cyclic diguanosine monophosphate (c-di-GMP). was unevenly distributed between the two progeny. c-di-GMP is a second messenger molecule. That finding was published in the journal Science in 2010.

Second messenger molecules transmit signals from sensors or receptors on the cell’s external membrane to targets within the cell, where they can rapidly alter a wide variety of cellular functions, such as metabolism and mobility. The ability to respond to external stimuli quickly is important for the bacteria’s survival. For instance, to stay alive, a bacterium must not  hesitate to  swim towards nutrients or away from toxins. This directional movement of microorganisms, spurred by the presence of a helpful or harmful substance, is known as chemotaxis.

“The effect of second messengers is almost immediate,” said Miller. “They allow bacteria to change their behavior within seconds.”

To detect the difference in c-di-GMP levels between cells, the researchers used a technique called Förster resonance energy transfer microscopy, or FRET microscopy. This allowed them to measure nanomolar changes of the concentration of c-di-GMP within individual bacteria as the changes happened second by second.

Different concentrations of c-di-GMP can have a profound influence on a cell’s behavior. For example, in the bacteria Pseudomonas aeruginosa, cells with high levels of c-di-GMP tend to remain still, adhere to surfaces and form colonies. Those with low levels, on the other hand, tend to actively swim about by using a corkscrew-shaped propeller located at one end of the bacterium.

In the latest study, the Miller and his colleagues worked out the molecular mechanism behind the difference in c-di-GMP concentrations seen between daughter cells.

When Pseudomonas cells divide, they pinch in half to create two daughter cells. Although the cells are genetically identical, only one daughter cell can inherit the bacterium’s single propeller. The other cell can synthesize its own propeller, but immediately after division the two cells are quite different.

What Miller and his coworkers report in the eLife paper is that the daughter cell that inherits the propeller also inherits an enzyme that is closely associated with the propeller that degrades c-di-GMP, as well as the organelle involved in directing  movement toward or away from stimuli that activates this enzyme.

Together these two organelles work in concert to lower the concentration of c-di-GMP and control swimming.

“What we have shown is that the uneven inheritance of organelles is another way cells have to create diversity and increase the chances of the survival of its species,” Miller said.

He added that his team’s findings may help explain how bacteria resist antibiotic treatments by always having some cells in their populations be in a slow-growing, resting state. Because antibiotics target fast-growing cells, these resting cells are more likely to survive the treatment. The findings might also help explain how some bacteria are able to adhere to and colonize surfaces such as urinary catheters, intravenous lines and heart valves.

In ongoing research, Miller’s team is trying to get a better understanding of the signals that can change second messenger concentrations very quickly and is screening compounds that could interfere with or alter those signals. Such compounds could be used to combat drug resistance, for instance, or inhibit a bacterium’s ability to adhere to surfaces and form slime-like colonies, called biofilms, that are highly resistant to antibiotics.

The new paper, as well as the earlier study, which appeared in the journal Science in 2010, are both available free online.

Kulasekara et al. c-di-GMP heterogeneity is generated by the chemotaxis machinery to regulate flagellar motility. 2013;2:e01402.

Chisten M et al.  Asymmetrical Distribution of the Second Messenger c-di-GMP upon Bacterial Cell Division. . 2010;  328(5983):1295-1297 DOI: 10.1126/science.1188658

The research was funded by the National Institute of Allergy and Infectious Diseases (Grant number: 5U54AI057141-09) the National Science Foundation Graduate Research Fellowship (Grant number 2007047910) and the National Institutes of Health (Grant number 1R21NS067579-0)

Read the mBio scientific

The research on drug-resistant E.coli was conducted by an  international collaborative research team that included Dr. Evgeni V. Sokurenko, 91̽�� professor of microbiology, as well as researchers at Group Health Clinical Laboratory and the Group Health Research Institute in Seattle.

Unlike previously identified superbugs that are usually from multiple strains, these E. coli bacteria belong to just one closely related clone.
“We now know that we are dealing with a single enemy, and that by focusing on this super-clone we can have a substantial impact on this worldwide epidemic,” Sokurenko said.

Over the past decade, public health officials noted that E. coli belonging to the ST131 strains family emerged as a major cause of urinary tract and kidney infections. These are the most common bacterial infection in women and elderly. The ST131 bacteria were notable because they had acquired resistance to a class of relatively new antibiotics called fluoroquinolones, which were commonly used to treat urinary tract infections.

More recently, theses pathogens also acquired genes for extended-spectrum beta-lactamase.
This change rendered a broad spectrum of antibiotics, including highly-potent penicillin derivatives and cephalosporins, ineffective against these strains of bacteria. As a result, the infections are increasingly difficult to treat.

These various resistant strains were assumed to have emerged independently around the world in response to their exposure to antibiotics.  But this was proven to be incorrect by the laboratories of Sokurenko and two other lead investigators on the study: Lance Price, professor of environmental and occupational health at the George Washington University School of Public Health and Health Services and an associate professor in the Pathogen Genomics Division of the Translational Genomics Research Institute in Arizona, and James R. Johnson, professor of Medicine at the Veterans Affairs Medical Center and the University of Minnesota.

In the new study, researchers sequenced the genomes of scores of ST131 bacterial samples collected from patients and animals around the world. Then, using a technique called whole-genome-sequence-based phylogenomic analysis, the researchers constructed a family tree that revealed the bacteria’s evolutionary history. That analysis indicated that almost all ST131 strains responsible for the notoriously resistant infections are very closely related to each other. They arise from a single clone that is termed H30-Rx for its resistance to treatment.

“Astoundingly, we found that all of the resistance could be traced back to a single ancestor,” said  Price “This superbug then took off, and now causes lots of drug-resistant infections.”

In addition, the H30-Rx strain is fast-growing and can spread from person to person. It infects both the healthy and infirm, young and old, and is adept at invading the bloodstream, said Sokurenko.

“In some hospitals it is responsible for up to half of E. coli infections. It is the most common single strain causing sepsis, a deadly form of blood infection that kills 20 percent to 40 percent of patients who develop it,” he said. “Due to its wide-spread resistance and virulence, the social and economic impact of H30-Rx clone could exceed that of any other bacterial strain known.”

According to James Johnson, the study’s findings may make it possible to develop “better tools to identify, stop or prevent its spread by finding better ways to block the transmission of the superbug, or by finding a
diagnostic test that would help doctors identify such an infection early on, before it might have the chance to turn lethal.”

In addition to the United States team, researchers from the Universitatsklinikum Munster in Muenster, Germany and the Statens Serum Institute in Copenhagen, Denmark participated in the study.

The research was supported by Office of Research and Development, Medical Research Service, Department of Veterans Affairs, Merit Review grant # 1 I01 CX000192 01488; the TGen Foundation; NIH grant RC4 AI092828; and USAMRMC grant W81XWH-10-1-0753.

In the paper, lead author Dr. Michael W. Schwartz, 91̽��professor of medicine and director of the Diabetes and Obesity Center of Excellence, and his colleagues from the universities of Cincinnati, Michigan, and Munich,  note that the brain was originally thought to play an important role in maintaining normal glucose metabolism  With the discovery of insulin in the 1920s, the focus of research and diabetes care shifted to almost exclusively to insulin. Today, almost all treatments for diabetes seek to either increase insulin levels or increase the body’s sensitivity to insulin.

“These drugs,” the researchers write, “enjoy wide use and are effective in controlling hyperglycemia [high blood sugar levels], the hallmark of type 2 diabetes, but they address the consequence of diabetes more than the underlying causes, and thus control rather than cure the disease.”

New research, they write, suggests that normal glucose regulation depends on a partnership between the insulin-producing cells of the pancreas, the pancreatic islet cells, and neuronal circuits in the hypothalamus and other brain areas that are intimately involved in maintaining normal glucose levels. The development of diabetes type 2, the authors argue, requires a failure of both the islet-cell system and this brain-centered system for regulating blood sugar levels .

In their paper, the researchers review both animal and human studies that indicate the powerful effect this brain-centered regulatory system has on blood glucose levels independent of the action of insulin. One such mechanism by which the system promotes glucose uptake by tissues is by stimulating what is called “glucose effectiveness.” As this process accounts for almost 50 percent of normal glucose uptake, it rivals the impact of insulin-dependent mechanisms driven by the islet cells in the pancreas.

The findings lead the researchers to propose a two-system model of regulating blood sugar levels composed of the islet-cell system, which responds to a rise in glucose levels by primarily by releasing insulin, and the brain-centered system that enhances insulin-mediated glucose metabolism while also stimulating glucose effectiveness.

The development of type 2 diabetes appears to involve the failure of both systems, the researchers say. Impairment of the brain-centered system is common, and it places an increased burden on the islet-centered system. For a time, the islet-centered system can compensate, but if it begins to fail, the brain-centered system may decompensate further, causing a vicious cycle that ends in diabetes.

Boosting insulin levels alone will lower glucose levels, but only addresses half the problem. To restore normal glucose regulation requires addressing the failures of the brain-centered system as well. Approaches that target both systems may not only achieve better blood glucose control, but could actually cause diabetes to go into remission, they write.

In addition to Schwartz, the authors of the Nature paper “Cooperation between brain and islet in glucose homeostasis and diabetes” are  Randy J. Seeley, Matthias H. Tscho, Stephen C. Woods, Gregory J. Morton, Martin G. Myers,  and David D’Alessio.

This work was partly funded by National Institutes of Health grants DK083042, DK093848 and DK089053, and the 91̽��Nutrition Obesity Research Center and Diabetes Research Center, and the Helmholtz Alliance  for Imaging and Curing Environmental Metabolic Diseases, through the Initiative and Networking Fund of the Helmholtz Association.

Treatment with two common drugs reduced viral replication and lung damage when given to monkeys infected with the virus that causes Middle East Respiratory Syndrome. The condition is deadly pneumonia that has killed more than 100 people, primarily in the Middle East.

Middle East Respiratory Syndrome, or MERS, was first reported in Saudi Arabia last year. The infection is caused by a coronavirus, called MERS-CoV, which is closely related to several coronaviruses that infect bats. About half of patients who developed the syndrome have died. Currently, there is no proven effective treatment.

The new findings show that a combination of interferon-alpha 2b and ribavirin, drugs routinely used to treat hepatitis C, may be an effective treatment for MERS-CoV infection, said Dr. Angela L. Rasmussen, a research scientist in the Department of Microbiology at the 91̽�� in Seattle and co-author of the study.

“Because these two drugs are readily available, they could be used immediately to treat patients infected with MERS-CoV,” Rasmussen said.

The study was conducted by researchers from the U.S. National Institute of Allergy and Infectious Diseases; the Universite Pierre et Marie Curie in Paris, France; the University of Manitoba in Winnipeg, Canada; and the 91̽�� in Seattle. The results were published online September 8 by the journal Nature Medicine. Darryl Falzarano, of the National Institute of Allergy and Infectious Diseases’s Rocky Mountain Laboratory in Hamilton, Mont.,  was the paper’s lead author.

Instead of directly targeting the virus like most conventional antivirals, these drugs work primarily by moderating the body’s immune response to the virus and by promoting repair of damaged lung tissue, said Rasmussen.

Working with the team of scientists in the 91̽��Viromics Lab, led by Dr. Michael Katze, 91̽��professor of microbiology, Rasmussen and her colleagues watched how the lung cells responded to the new treatment by tracking their gene expression profiles.

They did this by studying RNA extracted from the infected monkeys’ lungs to track changes in what is called the transcriptome. When a cell needs to use a gene, it copies the gene’s DNA-encoded instructions into RNA. That RNA transcript is then read to direct the assembly of a protein. With a “lab on a chip” technology, called a microarray, it is possible to detect and measure RNA transcripts from all the genes in a population of cells.  By analyzing the transcriptome, it is then possible to track how cells or a tissue respond to infection, a drug, or some other stimulus.   In this case, it allows researchers to study the host response to MERS-CoV in the context of the entire complex biological system, rather than one gene at a time.

Treatment interferon-alpha 2b and ribavirin appeared to have several interesting effects. It increased the transcription of genes that fight viral infections, for example, and it reduced transcription of genes that promote inflammation.  Of particular interest to Rasmussen and her colleagues, however, was the finding that treatment induced an increase in the transcription of genes that assist in regulating a protein called sonic hedgehog.

The sonic hedgehog protein helps moderate the immune response so that the response targets the virus more precisely. This precision reduces collateral damage from broader, less discriminate attack, and helps stimulate repair and growth of lung tissue.

During infection with many severe respiratory viruses, such as influenza, much of the damage is done, not by the virus, but by the body’s uncontrolled immune response to the virus, Rasmussen said.

The findings of this new study suggest that, in the case of MERS-CoV infections, interferon-alpha 3b and ribavirin may work primarily by reducing damaging inflammation of the lung and promoting healing by altering the host response, rather than directly targeting the virus.

If that is indeed true, other drugs that can similarly modulate the body’s reaction to viral infections may also prove to be effective against MERS-CoV and other infectious agents, she said.

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Read the Nature Medicine: Falzarano et al. Interferon-α2b and ribavirin treatment improves outcome in MERS-CoV-infected rhesus macaques.  Nature Medicine DOI: 10.1038/nm.3362 (2013).

The gene, PAX5, has long been known to be involved in acute lymphoblastic leukemia.  The new study indicates a mutation in the gene alone is sufficient to eventually cause the disease, which affects nearly 3,000 children and teenagers in the United States each year.

The discovery should make it possible to screen for the gene in families with a history of the disease and suggests new strategies for treating the disease, said Dr. Marshall Horwitz, professor of pathology and of medicine at the 91̽��. He is a co-author of the new study.

He was joined in the study by researchers at St. Jude Children’s Research Hospital in Memphis, Tennessee led by Dr. Charles Mullighan; Memorial Sloan-Kettering Cancer Center in New York City led by Dr. Kenneth Offit, and others at the UW. The results were published Sept. 8 in the journal Nature Genetics.

The researchers looked at the genes from two unrelated families that had a high rate of acute lymphoblastic leukemia and identified the same mutation of the PAX5 gene that ran in both the families.

This variant does not cause leukemia as long as it is paired with a normal version of the PAX5 gene, said Horwitz, but if the normal copy of the gene is lost and only the abnormal variant remains, some blood cells fail to become normally functioning white blood cells and, instead, turn into leukemia cells.

In the case of the families in the study, all the children who developed leukemia had damage to a chromosome in the affected blood cells. The damage, in which part of chromosome 9 was lost, removed the normal copy of the PAX5 gene. This left the abnormal gene unopposed.

PAX5 codes for a kind of protein, called a transcription factor, that plays a key role not only in blood cell maturation, but also in embryonic development.

“It was not a surprise that PAX5 turned out to be involved. It’s  the most commonly mutated gene found in ALL cells,” said Horwitz. “But it has not been clear whether PAX5 mutations were just mutations that had to happen at some point in the transformation of a normal cell to a leukemic cell or whether PAX5 variants were driving the leukemia.”

He said the findings indicate that PAX5 variants alone are sufficient to eventually cause acute lymphoblastic leukemia.

The finding has another important implication, said Horwitz. The fact that PAX5 is sufficient to cause acute lymphoblastic leukemia supports the concept that mutations that affect differentiation of blood cells are the key drivers of leukemia. If that is the case, it may be possible to design treatments that block de-differentiation or induce leukemic cells to re-differentiate so that they would begin to behave like normal cells again.

Such treatments might be more effective and have far fewer side effects than chemotherapy, the current standard treatment for these cancers, said Horwitz.

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Bacteria may draw other bacteria to a site of infection by laying down trails of a “molecular glue” that lead free-swimming individuals to come together and organize into colonies.

In the study, researchers were looking at how a species of bacteria called Pseudomonas aeruginosa attach and move about on surfaces. P. aeruginosa is a common cause of serious, often difficult-to-treat infections.

One reason they are so difficult to treat is their ability to mass together and surround themselves with matrix of proteins, DNA and polysaccharides, called a biofilm, that protects them from antibiotics and the body’s immune attack.

The study was the result of a collaboration of researchers from the University of California, Los Angeles, the 91̽�� in Seattle, and Northwestern University in Evanston, Illinois.

The findings were published May 8 in Nature in a titled, “Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms.”

Kun Zhao. from the UCLA Department of Bioengineering and Boo Shan Tseng from the 91̽��Department of Microbiology are the paper’s lead authors. The senior authors are Gerald C. L. Wong, professor of bioengineering at the California Nanosystems Institute at UCLA;  Matthew R. Parsek,  UW  professor of microbiology, and Erik Luitjen, at Northwestern University.

In earlier studies, the researchers had noticed that when individual, free-swimming P. aeruginosa attached themselves to glass and began to crawl along the surface they left a trail of a polysaccharide called Psl.

“This was surprising because in the bacterial world this is somewhat unusual,” said Parsek,. “And it looked cool. But the question was whether it was biologically important.”

For this study, the researchers used a specially designed chamber that allowed them to watch how free-swimming P. aeruginosa attached to and moved about on a glass surface. They then used video microscopy to track and analyze the behavior the bacteria.

“Some of the bacteria remained fixed in position,” said Parsek. “But some moved around on the surface, apparently randomly but leaving a trail that influenced the surface behavior of other bacteria that encountered it.”

Once enough of the bacteria had gathered, about 50 or so, their behavior changed: they abandoned their wandering ways and began to organize into small structures called micro-colonies, the first step in biofilm formation.

If there are ways to inhibit the formation of these trails or block their effect, it may be possible to inhibit the formation of biofilms, Parsek said. This might help prevent infections or make them easier to treat.

The researchers are also interested to learn whether other bacterial species also take these polysaccharide trails as a signal to congregate. Pseudomonas infections often involve other bacterial species and this might explain how these polymicrobial infections get started.

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The 91̽��portion of the study was supported by National Institutes of Health grants R01HL087920, R01AI077628, R01AI081983, R56AI061396 and National Science Foundation grant MCB0822405.

91̽��Medicine will launch a multi-media initiative April 1 to provide consumers with health and wellness information. In partnership with Fisher Communications, 91̽��Medicine also will increase awareness of the latest treatments and medical breakthroughs at 91̽��Medicine.

“In support of our mission to improve the health of the public, 91̽��Medicine recognizes the need to encourage each member of our community to take responsibility for their personal health,” said Dr. Paul G. Ramsey, CEO of 91̽��Medicine. “With this initiative, our audiences will gain valuable knowledge and tools for engaging in preventive care and establishing rewarding personal health behaviors.”

“The new initiative is part of 91̽��Medicine’s overall strategy to provide comprehensive care for our community,” said Johnese Spisso, 91̽��Medicine’s chief health system officer. “It will highlight 91̽��Medicine’s expertise in a broad range of primary care and specialty fields while helping consumers make informed decisions about their treatment options in our health system.”

Look for:

• Regular television and radio spots featuring 91̽��Medicine experts and patients.on Fisher Communication’s KOMO News, KOMO News Radio and STAR 101.5. Topics for the first three months include heart, vascular and brain health.

• A new dedicated website, 91̽��Medicine Health, . It will have timely news items, features and columns about health and wellness, medical research advances and patient stories.

KOMO news anchor Molly Shen will introduce the program to viewers and listeners of KOMO News, KOMO News Radio and Star 101.5. The first series of TV and radio spots on heart health will begin April 8. During these segments, 91̽��Medicine experts and patients will share stories and insights about the care they received at 91̽��Medicine.

This month’s articles on heart health include:

• 91̽��Medicine Regional Heart Center leads in heart care.
• How to reduce your risk of coronary artery disease.
• New defibrillator for treating heart rhythm disorders.
• Multi-specialty care saves a triathlon runner with heart disease.

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For more information, contact 91̽��Medicine Strategic Marketing & Communications at 206-543-3620.