WASHINGTON, DC - November 13, 2014 -- The strains of enterotoxigenic Escherichia coli (ETEC) that infect adults and children in Asia, Africa, and the Americas, have notably similar toxins and virulence factors, according to research published ahead of print in the Journal of Bacteriology. That bodes well for vaccine development, says corresponding author Åsa Sjöling, now of the Karolinska Institutet, Stockholm, Sweden. ETEC infects 400 million people annually, or 5.3 percent of the world's population, killing 400,000.
In the study, Sjöling et al. set out to determine whether the heat labile toxin (LT) had become more toxic over time, and whether the bacterium had evolved to secrete more of it. LT causes the "travelers' diarrhea" that so frequently afflicts Americans abroad, and that plagues residents of many low and middle income countries. But they found that over the 30 year period from which they had isolates, the two most potent toxin types, LT1 and LT2, had changed little but had spread globally.
"When new ETEC strains acquire either LT1 or LT2 they seem to have a much better chance to persist and spread," says Sjöling. Colonization factors, the compounds the bacterium uses to adhere to the lining of the human got, also remained conserved over time, and the most common colonization factors identified globally were often associated with LT1 and LT2.
The research results from a collaboration between the University of Gothenburg (where Sjöling did this research), which has the world's largest collection of ETEC strains, and sequencing experts at the Sanger Institute, Cambridge, UK. "We soon saw that strains with similar toxin variants and colonization factor profiles often remained closely related despite having been isolated on different continents, with time spans between those isolations ranging up to 30 years," says Sjöling.
The paper is published concurrently with a paper in Nature Genetics by many of the same authors. In that paper, investigators developed whole-genome sequence data for 362 ETEC strains over 30 years, in 20 countries. "This research strengthens our belief that it is possible to target a broad range of ETEC groups with one vaccine," says Gordon Dougan of the Sanger Institute, a coauthor of both papers.
"We believe that the vaccine developed at the University of Gothenburg will be protective and useful globally since this vaccine is based on the toxin types and colonization factors we found to be most successful worldwide," says Sjöling.
While ETEC was believed to vary widely from place to place, the Nature Genetics investigators traced many of the 21 lineages to an individual bacterium that acquired the genetic information needed to infect humans between 51 and 174 years ago, and then spread. That, in turn, suggests that the bacterium is stable, and that it is unlikely to become vaccine-resistant, and that the vaccine will be effective worldwide in both children and adults, says Sjöling.
Journal of Bacteriology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
WASHINGTON, DC - November 18, 2014 - Certain subtypes of avian influenza viruses have the potential to cause more severe disease in humans than other avian influenza subtypes and should be monitored carefully to prevent spread of disease, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology.
The work, directed by researchers at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., found that flu viruses expressing the low pathogenicity avian H1, H6, H7, H10 or H15 hemagglutinins (genes that encode the major surface protein for the virus) led to fatal infections in mice and caused more cell damage in normal human lung cells grown in culture as compared to avian influenza viruses with other subtypes. The 1918 H1 subtype hemagglutinin has been already identified as a key virulence factor in the pandemic influenza virus of 1918. That virus, which caused the so-called "Spanish flu," spread rapidly around the world, resulting in approximately 50 million deaths.
"Viruses with these avian hemagglutinins have some type of inherent virulence motif to them, in that they induce a marked inflammatory response in mammals including human cells in culture," said senior study author Jeffery K. Taubenberger, MD, PhD, chief of the Viral Pathogenesis and Evolution Section of NIAID's Laboratory of Infectious Diseases. In 2013-2014 there have been close to 400 cases of avian influenza H7N9 infections in people in China, many severe, along with small numbers of severe human infections with H10N8 and H6N1 subtypes. "From a public health and epidemiology standpoint, it's useful to know that avian viruses of these subtypes (for example, H6, H7, or H10) might lead to more severe infections in humans and is something to look out for."
In a specialized laboratory , Taubenberger and colleagues developed a series of viruses mimicking 13 subtypes of contemporary low pathogenicity avian influenza A viruses. Each avian influenza virus tested was genetically identical to each other except that they expressed different hemagglutinin subtypes. After growing the viruses in culture, the researchers inoculated them into mice and watched to see what would happen. This approach allowed a direct comparison of the role of different hemagglutinins in virulence.
The viruses expressing the H1, H6, H7, H10 and H15 subtypes all caused rapid weight loss and fatal pneumonia infections within a week. By contrast, the H2, H3, H5, H9, H11, H13, H14 and H16-expressing viruses caused only mild weight loss but no significant disease.
The research team performed a similar test using hemagglutinins from two 2013 H7N9 flu viruses from outbreaks in Anhui and Shanghai, China, with similar results in mice. They also took a subset of these viruses and put them in culture with normal human lung cells that line the airways. The cells had developed into a thick layer called an epithelium. The disease-causing viruses like H1 and H7 caused mature cells to rapidly die over a couple of days, leaving just a thin lining behind.
These results suggest that hemagglutinins may not require immune cells to trigger cell damage but instead may cause programmed cell death or other molecular processes that could ultimately lead to enhanced disease or fatalities, Taubenberger said. In the future it will be important to tease out the differences in the hemagglutinins' structural features and investigate the molecular processes involved as the viruses infect mammalian cells, he said.
Meanwhile, until more is understood about how flu viruses cross from animals to humans and spread, more research is needed into producing a more broadly protective "universal" flu vaccine that may ultimately offer the best protection against future pandemics, he said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the Defense Threat Reduction Agency. The article can be found online at [URL to come].
mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online athttp://mbio.asm.org.
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
WASHINGTON, DC – October 7, 2014 -- Yogurt containing probiotic bacteria successfully protected children and pregnant women against heavy metal exposure in a recent study. Working with funding from the Bill and Melinda Gates Foundation, Canadian and Tanzanian researchers created and distributed a special yogurt containing Lactobacillus rhamnosus bacteria and observed the outcomes against a control group. The work is published this week in mBio®, the online open-access journal of the American Society for Microbiology.
A research team from the Canadian Centre for Human Microbiome and Probiotics, led by Dr. Gregor Reid, studied how microbes could protect against environmental health damage in poor parts of the world. Their lab research indicated that L. rhamnosus had a great affinity for binding toxic heavy metals. Working with this knowledge, the team hypothesized that regularly consuming this probiotic strain could prevent metals from being absorbed from the diet.
Working with the Western Heads East organization, Dr. Reid had already established a network of community kitchens in Mwanza, Tanzania to produce a probiotic yogurt for the local population. Mwanza is located on the shores of Lake Victoria, which is known to be polluted with pesticides and toxic metals including mercury. The team utilized this network to produce and distribute a new type of yogurt containing L. rhamnosus. The special yogurt was distributed to a group of pregnant women and a group of children. The researchers measured the baseline and post-yogurt levels of toxic metals.
The team found a significant protective effect of the probiotic against mercury and arsenic in the pregnant women. This is important as “reduction in these compounds in the mothers could presumably decrease negative developmental effects in their fetus and newborns,” according to Dr. Reid. While the results obtained in the children studied showed benefits and lower toxin levels, the sample size and duration of treatment did not allow statistical significance.
The researchers were excited by the potential of basic foodstuffs to provide preventative protection for pregnant women worldwide. They are currently investigating lactobacilli with higher and even more specific mechanisms of sequestering mercury.
American Society for Microbiology and UNC Charlotte’s Atkins Library Deliver Perpetual Unlimited Access to E-Textbooks for Authorized Users
Washington DC – October 28, 2014 -- The American Society for Microbiology (ASM) Press and the J. Murrey Atkins Library at UNC Charlotte announced today that they are experimenting with an innovative business model that will deliver affordable e-textbooks to students and faculty.
This fall, Atkins Library purchased perpetual access to the ASM Press e-textbook, Scientific Integrity. With the cooperation of ASM Press, the library arranged to purchase unlimited concurrent user access to the title, which had been adopted for use in a graduate level courses, for its students and faculty. The price is based on one year of expected student enrollment, but provides permanent access to the book for the library.
Scientific Integrity has been adopted by a UNC Charlotte course entitled “Professionalism and the Responsible Conduct of Research”. Taught by Dr. Jo Ann Lee, Faculty Associate for Graduate Research and Ethics in the Center for Graduate Life at UNC Charlotte, the course focuses on the nine areas of ethical behavior for which training is required by the National Institutes of Health (NIH) and the National Science Foundation (NSF).
Professor Lee had this to say about the arrangement, "I was thrilled when I learned that my students would have free access to our course textbook, Scientific Integrity. Typically, a few students of past semesters had to wait for print copies to arrive before they could complete assignments. With the e-textbook, there were no glitches, and Atkins Library made it easy to access for my students by posting it on the course Moodle page."
ASM Press Director Christine Charlip suggests that this model will work for any institution that wants to add e-textbooks to its learning management systems and e-course reserves, provided the institution has the technological infrastructure to limit use to authorized users only, such as faculty and enrolled students. Unlimited concurrent user access allows an institution to avoid the additional costs and inconvenience that result from limitations on concurrent users for titles purchased through traditional e-book distributors.
Ms. Charlip commented, “We are interested in finding innovative ways to promote the use of e-textbooks among students and the adoption of e-textbooks by faculty while remaining sensitive to student cost. Knowing that UNC Charlotte would securely host the PDF file made this collaboration possible.”
Charles Hamaker, Associate University Librarian for Collection Development and Electronic Resources, said that e-textbooks are typically bought or rented directly by the students, but in this case, the university decided to support the purchase. “Buying more than a couple of ‘seats’ for an e-textbook generally increases the price considerably without providing the wide access for students and faculty that we want to offer. Plus, you have to keep buying that access year after year. With this ground-breaking model, our patrons, as well as the library budget, benefit.”
Institutions or individuals who wish to know more about innovative ways to supply e-textbooks to readers are encouraged to contact Ms. Charlip (email@example.com) or Mr. Hamaker (firstname.lastname@example.org).
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
UNC Charlotte is North Carolina’s urban research university. It leverages its location in the state’s largest city to offer internationally competitive programs of research and creative activity, exemplary undergraduate, graduate, and professional programs, and a focused set of community engagement initiatives. UNC Charlotte maintains a particular commitment to addressing the cultural, economic, educational, environmental, health, and social needs of the greater Charlotte region.
WASHINGTON, DC – OCTOBER 13, 2014 - A robust, broad spectrum antibiotic, and a gene that confers immunity to that antibiotic are both found in the bacterium Staphylococcus epidermidis Strain 115. The antibiotic, a member of the thiopeptide family of antibiotics, is not in widespread use, partly due to its complex structure, but the investigators, from Brigham Young University, Provo, Utah, now report that the mechanism of synthesis is surprisingly simple. “We hope to come up with innovative processes for large-scale production and derivitization so that new, and possibly more potent versions of the antibiotic can become available, says co-corresponding author Joel S. Griffitts. The research is published ahead of print in Journal of Bacteriology.
Strain 115 was originally discovered on turkeys that appeared to have enhanced immunity to bacterial infections. “The motivation behind our current work was a desire to understand the connection between Strain 115 and immunity to disease-causing bacteria,” says Griffitts.
It quickly became clear to the investigators that Strain 115 could produce a potent antibiotic that targets a large number of medically relevant bacteria, including those that cause staph infections, strep throat, and severe gastrointestinal diseases. “We wanted to know the identity of this antibiotic and the means by which Strain 115 protects itself from its own antibiotic’s deadly effects,” says Griffitts.
“We found that the genes for both antibiotic synthesis and self protection in Strain 115 are conveniently clustered on a compact DNA molecule [a plasmid] that replicates itself as a small circle within the cells of Strain 115,” says Griffitts. Among experiments they conducted to prove this, they engineered a version of Strain 115 that was missing the plasmid. That version failed to produce both the antibiotic and the immunity to the antibiotic.
The investigators then analyzed the mechanism of immunity. “Thiopeptide antibiotics kill cells by blocking a part of the ribosome,” Griffitts explains. Ribosomes, common to all living organisms, are the machines that read the genetic code, producing proteins based on the instructions therein. The plasmid, which directs the production of the thiopeptide antibiotic, also directs production of a spare part for the ribosome, a replacement for the part that is blocked by the antibiotic, which renders the ribosome insensitive to the antibiotic.
The investigation of Strain 115 began as an undergraduate project, after the bacteria had sat in a laboratory freezer for decades, says Griffitts. “It quickly grew into an effort involving two Ph.D. microbiologists, a talented graduate student, and several analytical biochemists.” Hopefully, he says, the research will ultimately enable production of a valuable antibiotic, in quantities sufficient to make a dent in the antibiotic crisis.