Ebola, Marburg viruses edit genetic material during infection

WASHINGTON, DC – November 4, 2014 – Filoviruses like Ebola “edit” genetic material as they invade their hosts, according to a study published this week in mBio®, the online open-access journal of the American Society for Microbiology. The work, by researchers at the Icahn School of Medicine at Mount Sinai, the Galveston National Laboratory, and the J. Craig Venter Institute, could lead to a better understanding of these viruses, paving the way for new treatments down the road.

Using a laboratory technique called deep sequencing, investigators set out to investigate filovirus replication and transcription, processes involved in the virus life cycle. They studied the same Ebola virus species currently responsible for an outbreak in West Africa, and also analyzed a related filovirus, Marburg virus, that caused a large outbreak in Angola in 2005 and recently emerged in Uganda. The scientists infected both a monkey and human cell line with both viruses, and analyzed the genetic material produced by each virus, called RNA.

Their results highlight regions in Ebola and Marburg virus RNAs where the polymerase of the virus (a protein that synthesizes the viral RNA) stutters at specific locations, adding extra nucleotides (molecules that form the building blocks of genetic material like DNA and RNA), thereby “editing” the new RNAs. The study found new features at a described RNA editing site in the Ebola glycoprotein RNA, which makes the protein that coats the surface of the virus. Their work also identified less frequent but similar types of editing events in other Ebola and Marburg virus genes – the first time this has been demonstrated. Because of these messenger RNA modifications, Ebola and Marburg are potentially making proteins “that we previously didn’t realize,” said Christopher F. Basler, PhD, senior study author and professor of microbiology at Mount Sinai. Continue reading “Ebola, Marburg viruses edit genetic material during infection”

Virus kills melanoma in animal model, spares normal cells

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Researchers from Yale University School of Medicine have demonstrated that vesicular stomatitis virus (VSV) is highly competent at finding, infecting, and killing  human melanoma cells, both in vitro and in animal models, while having little propensity to infect non-cancerous cells.

“If it works as well in humans, this could confer a substantial benefit on patients afflicted with this deadly disease,” says Anthony van den Pol, a researcher on the study. The research was published online ahead of print in the Journal of Virology.

Most normal cells resist virus infection by activating antiviral processes that protect nearby cells. “The working hypothesis was that since many cancer cells show a deficient ability to withstand virus infection, maybe a fast-acting virus such as VSV would be able to infect and kill cancer cells before the virus was eliminated by the immune system,” says van den Pol. And indeed, the virus was able to selectively infect multiple deadly human melanomas that had been implanted in a mouse model, yet showed little infectivity towards normal mouse cells, he says.

Many different mechanisms are involved in innate immunity, the type of immunity that combats viral infection. van den Pol plans to investigate which specific mechanisms are malfunctioning in cancer cells, knowledge that would be hugely beneficial both in understanding how cancer affects immunity, and in enhancing a virus’ ability to target cancer cells, he says.

Melanoma is the most deadly skin cancer. Most melanomas are incurable once they have metastasized into the body. The incidence of melanoma has tripled over the last three decades, and it accounts for approximately 75 percent of skin cancer-related deaths.

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A copy of the manuscript can be found online at http://bit.ly/asmtip0413b.  Formal publication is scheduled for the June 2013 issue of the Journal of Virology.

(G. Wollmann, J.N. Davis, M.W. Bosenberg, and A.N. van den Pol, 2013. Vesicular stomatitis virus variants selectively infect and kill human melanomas but not normal melanocytes. J. Virol.  Published ahead of print 3 April 2013 , doi:10.1128/JVI.03311-12)

Journal of Virology 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.

High-salt diet and ulcer bug combine to increase risk of cancer : ” Every animal on the high salt diet developed cancer “

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Numerous epidemiologic studies have shown that a diet high in salt is associated with an increased risk of gastric cancer. Now Timothy L. Cover and colleagues of Vanderbilt University show that high dietary salt combined with infection by the ulcer-causing bacterium Helicobacter pylori greatly increases the risk of cancer.  The study was published ahead of print in the journal Infection and Immunity.

In the study, the researchers infected Mongolian gerbils with H. pylori. One set of gerbils received a regular diet; the other, a high salt diet. At the end of the experiment the researchers analyzed the animals’ stomach tissues. Every animal on the high salt diet developed cancer, compared with just 58 percent of those on the regular diet.

It appears development of gastric cancer required the presence of a particular bacterial oncoprotein, known as CagA, which is produced by H. pylori. Gastric cancer did not develop in animals on the high salt diet that were infected with a mutant H. pylori which did not produce CagA. In earlier studies, Cover and others had shown that culturing H. pylori in a high salt environment boosts production of CagA. “This was one of the driving forces that led us to undertake the current studies,” says Cover.

The investigators note that while no studies, to their knowledge, have examined relationships among a high salt diet, and infection with H. pylori expressing cagA, “in several parts of the world that have high rates of gastric cancer, there is a high prevalence of cagA+ strains and a large proportion of the population consumes a high-salt diet.”

The investigators also detected significantly higher levels of gastric inflammation in H. pylori-infected gerbils on a high salt diet than in those on a regular diet, a finding which Cover says is relevant to many types of cancer. They also showed that transcription of various inflammatory cytokines, such as interleukin 1-beta, are elevated in the former as compared to the latter, suggesting that “these factors may contribute to the increased inflammation and increased gastric risk that accompany a high salt diet,” says Cover.

At least 50 percent of humans are infected with H. pylori, at least 90 percent of them without symptoms.

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A copy of the manuscript can be found online at http://bit.ly/asmtip0413a.  Formal publication is scheduled for the June 2013 issue of Infection and Immunity.

(J.A. Gaddy, J.N. Radin, J.T. Loh, F. Zhang, M.K. Washington, R.M. Peek, Jr., H.M.S. Algood, and T.L. Cover, 2013. High dietary salt intake exacerbates Helicobacter pylori-induced gastric carcinogenesis. Infect. Immun.  Publish ahead of print 8 April 2013 , doi:10.1128/IAI.01271-12.)

Infection and Immunity 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.

Mutation altering stability of surface molecule in acid enables H5N1 infection of mammals

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

A single mutation in the H5N1 avian influenza virus that affects the pH at which the hemagglutinin surface protein is activated simultaneously reduces its capacity to infect ducks and enhances its capacity to grow in mice according to research published ahead of print today in the Journal of Virology.

“Knowing the factors and markers that govern the efficient growth of a virus in one host species, tissue, or cell culture versus another is of fundamental importance in viral infectious disease,” says Charles J. Russell of St. Jude Children’s Research Hospital, Memphis, TN, an author on the study. “It is essential for us to identify influenza viruses that have increased potential to jump species, to help us make decisions to cull animals, or quarantine humans.” The same knowledge “will help us identify targets to make new drugs that stop the virus… [and] engineer vaccines.”

Various influenza viruses are spreading around the globe among wild birds, but fortunately, few gain the ability to jump to humans. However, those that do, and are able to then spread efficiently from person to person, cause global epidemics, such as the infamous pandemic of 1918, which infected one fifth and killed an estimated 2.7 percent of the world’s population. Occasionally, one of these viruses is exceptionally lethal. For example, H5N1 has killed more than half of the humans it has infected. The specter of such a virus becoming easily transmissible among humans truly frightens public health officials. But understanding the mechanisms of transmission could help microbiologists find ways to mitigate major epidemics.

When influenza viruses infect birds, the hemagglutinin surface protein of the virus is activated by acid in the entry pathway inside the host cell, enabling it to invade that cell. In earlier work, Russell and collaborators showed that a mutant version of the influenza H5N1 virus called K58I that resists acid activation, loses its capacity to infect ducks. Noting that the upper airways of mammals are more acidic than infected tissues of birds, they hypothesized, correctly, that a mutation rendering the hemagglutinin protein resistant to acid might render the virus more infective in mammals.

In this study the investigators found that K58I grows 100-fold better than the wild-type in the nasal cavities of mice, and is 50 percent more lethal. Conversely, the mutant K58I virus failed completely to kill ducks the investigators infected, while the wild-type killed 66 percent of ducks, says Russell. “A single mutation that eliminates H5N1 growth in ducks simultaneously enhances the capacity of H5N1 to grow in mice. We conclude that enhanced resistance to acid inactivation helps adapt H5N1 influenza virus from an avian to a mammalian host.”

“These data contribute new information about viral determinants of influenza virus virulence and provide additional evidence to support the idea that H5N1 influenza virus pathogenesis in birds and mammals is linked to the pH of [hemagglutinin] activation in an opposing fashion,” Terence S. Dermody of Vanderbilt University et al. write in an editorial in the journal accompanying the paper. “A higher pH optimum of [hemagglutinin] activation favors virulence in birds, whereas a lower pH optimum… favors virulence in mammals.”

Based on this and another study, “…surveillance should include phenotypic assessment of the [hemagglutinin] activation pH in addition to sequence analysis,” Dermody writes.

The journal carefully considered whether to publish the paper, because it raised issues of “dual use research of concern” (DURC), writes Dermody. DURC is defined as “Life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security,” according to a US government policy document. However, both the National Institute of Allergy and Infectious Diseases and the St. Jude Institutional Biosafety Committee concluded that the study failed to meet the definition of DURC. Clinching the case, “the addition of the key mutation in the Russell paper to other previously reported mutations would not result in an even more virulent H5N1 influenza virus,” says Dermody.

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A copy of the research manuscript can be found online at http://bit.ly/asmpr0213b.  The manuscript of the accompanying editorial can be accessed at http://bit.ly/asmpr0213c. Both are scheduled to be formally published in the May 2013 issue of the Journal of Virology.

(H. Zaraket, O.A. Bridges, and C.J. Russell, 2013. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J. Virol. online ahead of print February 28, 2013, doi:10.1128/JVI.03110-12.)

The Journal of Virology 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.

Good bacteria may expunge vancomycin-resistant bacteria from your gut

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Probiotic possibilities loom

Too much antibiotic can decimate the normal intestinal microbiota, which may never recover its former diversity. That, in turn, renders the GI tract vulnerable to being colonized by pathogens. Now researchers from Memorial Sloan-Kettering Cancer Center, New York, NY, and Centro Superior de Investigación en Salud Pública, Valencia, Spain, show that reintroducing normal microbial diversity largely eliminated vancomycin-resistant enterococci (VRE) from the intestinal tracts of mice. The investigators showed further that the findings may apply to humans. The research is published in the March 2013 issue of the journal Infection and Immunity.

The reduced diversity of microbiota wrought by antibiotics “allow[s] VRE to invade and thrive in the intestine, suggesting that bacterial species that are wiped out by antibiotics are key to preventing colonization by VRE,” says first author Carles Ubeda of the Centro Superior de Investigacion en Salud Publica, Valencia, Spain. “We hypothesized that repopulating the mice’ intestines with the missing bacteria would promote clearance of the VRE.”

In the study, the researchers treated mice with antibiotics. They then gave the mice fecal transplants from untreated mice, or aerobic or anaerobic cultures from the fecal transplants. Following the latter treatments, mice receiving the fecal transplant or the anaerobic culture were able to clear the VRE, while those receiving the aerobic culture failed to do so. The researchers compared the microbiota in each group. The big difference: the mice that had cleared the VRE contained bacteria from the anaerobic genus, Barnesiella, while those that had failed to clear the VRE did not.

The researchers then analyzed the fecal microbiota from human patients who had received bone marrow transplants, who were at high risk of being colonized by vancomycin-resistant enterococci. “The presence of Barnesiella in fecal samples was associated with protection against VRE, suggesting that in humans, Barnesiella may also confer protection against dense VRE colonization,” says Ubeda.

“The findings could be very useful for development of novel probiotics,” says Ubeda. Additionally, “scientifically, this is a major finding that will help us to understand how the microbiota confer resistance against intestinal colonization by pathogens, an important question that remains incompletely answered.”

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(C. Ubeda, V. Bucci, S. Caballero, et al. Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect. Immun. 81:965-973)

Infection and Immunity 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

Skin, soft tissue infections succumb to blue light : 100% Survival of Infections Vs. 18%

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Blue light can selectively eradicate Pseudomonas aeruginosa infections of the skin and soft tissues, while preserving the outermost layer of skin, according to a proof-of-principle study led by Michael R. Hamblin of the Massachusetts General Hospital, and the Harvard Medical School, Boston. The research is published online ahead of print in the journal Antimicrobial Agents and Chemotherapy

“Blue light is a potential non-toxic, non-antibiotic approach for treating skin and soft tissue infections, especially those caused by antibiotic resistant pathogens,” says Hamblin.

In the study, animal models were infected with P. aeruginosa. All of the animals in the group treated with blue light survived, while in the control, 82 percent (9 out of 11) of the animals died.

Skin and soft tissue infections are the second most common bacterial infections encountered in clinical practice, and represent the most common infection presentation—more than 3 percent—in patients visiting emergency departments, says Hamblin. The prevalence of skin and soft tissue infections among hospitalized patients is 10 percent, with approximately 14.2 million ambulatory care visits every year and an annual associated medical cost of almost $24 billion (equivalent to $76 for every American), says Hamblin.

Treatment of skin and soft tissue infections has been significantly complicated by the explosion of antibiotic resistance, which may bring an end to what medical scientists refer to as the antibiotic era, says Hamblin. “Microbes replicate very rapidly, and a mutation that helps a microbe survive in the presence of an antibiotic drug will quickly predominate throughout the microbial population. Recently, a dangerous new enzyme, NDM-1, that makes some bacteria resistant to almost all antibiotics available has been found in the United States. Many physicians are concerned that several infections soon may be untreatable.”

Besides harming public health, antibiotic resistance boosts health care costs. “Treating resistant skin and soft tissue infections often requires the use of more expensive, or more toxic drugs, and can result in longer hospital stays for infected patients,” says Hamblin.

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A copy of the manuscript can be found online at http://bit.ly/asmtip0113b. Formal publication of the paper is scheduled for the March 2013 issue of Antimicrobial Agents and Chemotherapy.

(T. Dai, A. Gupta, Y.-Y. Huang, R. Yin, C.K. Murray, M.S. Vrahas, M. Sherwood, G.P. Tegos, and M.R. Hamblin, 2013. Blue light rescues mice from potentially fatal Pseudomonas aeruginosa burn infection: efficacy, safety, and mechanism of action. Antim. Agents Chemother. Published ahead of print 21 December 2012 ,doi:10.1128/AAC.01652-12)

Antimicrobial Agents and Chemotherapy 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

Pigs in southern China infected with avian flu: Recent Infections of H1N1 & H3N2

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Researchers report for the first time the seroprevalence of three strains of avian influenza viruses in pigs in southern China, but not the H5N1 avian influenza virus.  Their research, published online ahead of print in the Journal of Clinical Microbiology, has implications for efforts to protect the public health from pandemics.

Influenza A virus is responsible both for pandemics that have killed millions worldwide, and for the much less severe annual outbreaks of influenza. Because pigs can be infected with both human and avian influenza viruses, they are thought to serve as “mixing vessels” for genetic reassortment that could lead to pandemics, and pigs have been infected experimentally by all avian H1-H13 subtypes. But natural transmission of avian influenza to pigs has been documented only rarely.

In the study, from 2010-2012, Guihong Zhang and colleagues of the College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China, tested 1080 21-25 week old pigs for H3, H4, H5, and H6 subtypes of avian influenza virus, and H1 and H3 subtypes of swine influenza virus. Thirty-five percent of the serum samples were positive for H1N1, and 19.7 percent were positive for H3N2 swine flu virus, and 0.93 percent, 1.6 percent, and 1.8 percent were positive, respectively, for the H3, H4, and H6 subtypes of avian influenza A virus. However, no serum samples collected in 2001 were positive for any of these viruses, indicating that transmission into swine was recent.

Given the recent transmission of avian influenzas into swine, “We recommend strongly that the pork industry worldwide should monitor the prevalence of influenza in pigs, considering their important role in transmitting this virus to humans,” says Zhang.

Previously, novel reassortant H2N3 influenza viruses were isolated from US pigs, which “were infectious and highly transmissible in swine and ferrets without prior adaptation,” according to a 2009 paper in the Journal of Molecular and Genetic Medicine by Wenjun Ma et al. Those viruses resembled, but were not identical to the H2N2 human pandemic virus of 1957.

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A copy of the manuscript can be found online at http://bit.ly/asmtip1212d.  Formal publication is scheduled for the February 2013 issue of the Journal of Clinical Microbiology.

(S. Su, W. Qi, J. Chen, W. Zhu, Z. Huang, J. Xie, and G. Zhang, 2012. Seroepidemiological evidence of avian influenza A virus transmission in pigs in southern China. J. Clin. Microbiol. Online ahead of print 21 November 2012.)

The Journal of Clinical Microbiology 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.

Research on enhanced transmissibility in H5N1 influenza: Should the moratorium end?

Public Release: 9-Oct-2012

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

How can scientists safely conduct avian flu research if the results could potentially threaten, as well as save, millions of lives? In a series of commentaries appearing on Tuesday, October 9 in mBio®, the online open-access journal of the American Society for Microbiology, prominent microbiologists and physicians argue the cases both for and against lifting a voluntary moratorium on experiments to enhance the ability of the H5N1 virus to move from mammal to mammal, so-called “gain-of-function” research, and discuss the level of biosecurity that would be appropriate for moving that research forward.

In January 2012, in response to the controversy caused by the unprecedented recommendation iof an advisory board to the government to redact methods sections  of two research studies showing how genetic changes could make H5N1 become transmissible between mammals, a group of influenza researchers agreed to a voluntary pause on any research involving highly pathogenic avian influenza H5N1 viruses leading to the generation of viruses that are more transmissible in mammals. Despite both articles eventually being published in full in May and June 2012, the research moratorium remains in place.

“The scientific community and the greater society that it serves are currently engaged in a vigorous debate on whether and how to carry out experiments that could provide essential information for preparedness against a pandemic of avian influenza. To foster discussion and to provide a venue to record the arguments for or against this moratorium, mBio® has commissioned a series of views from experts in the field,” write Arturo Casadevall of the Albert Einstein School of Medicine, editor-in-chief of mBio®; and Thomas Shenk of Princeton University, Chair of the ASM Publications Board, in an introductory editorial.

Enhancing and analyzing the transmissibility of the H5N1 virus could, on the one hand, provide insights that could help prevent or treat a future outbreak of H5N1 , or, on the other hand, it may provide a roadmap for a “bad actor” to deliberately bring about an influenza pandemic or lead to an inadvertent release of a virus with enhanced transmissibility.

Authors of the commentaries are prominent scientists, including:

  • Ron Fouchier of Erasmus MC Rotterdam in The Netherlands, Adolfo García-Sastre of the Mount Sinai School of Medicine, and Yoshihiro Kawaoka of the University of Wisconsin-Madison, lead authors of the two papers that began the controversy, argue that in the eight months since the moratorium was agreed upon, the international research community has had sufficient time to review biosafety and biosecurity measures and that H5N1 transmission studies ought to proceed. 
  • Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases contributes his voice as a representative of an organization that is a key funder of influenza research. Although Fauci acknowledges that the benefits of gain-of-function research outweigh the risks, he argues that scientists have yet to fully meet their responsibility for engaging the public in weighing these matters and making the case for proceeding. He outlines how the U.S. government plans to augment policy guidelines related to “dual use research of concern” like the experiments on enhanced influenza transmission. 
  • Marc Lipsitch and Barry R. Bloom of the Harvard School of Public Health explain why they view H5N1 with enhanced transmissibility as a “potential pandemic pathogen,”representing an even greater threat to global health than Ebola and other biosafety level 4 (BSL-4) pathogens. They argue that research on enhanced H5N1 and other potential pandemic pathogens requires a new, more stringent set of guidelines for safety, thorough public discussion of the risks and benefits involved, and global guidelines for laboratory procedures, among other measures to minimize the risk of laboratory-released infections or epidemics. 
  • Ian Lipkin of Columbia University argues that once research on enhanced strains of H5N1 continues it may be advisable to conduct the work only in BSL-3 Ag laboratories that meet additional, enhanced guidelines for handling agents with pandemic potential. Lipkin proposes that any course should be charted in consultation with and oversight from the global scientific and regulatory community. 
  • Stanley Falkow of Stanford University provides perspective on the H5N1 research moratorium based on his own experiences with a similar situation in the 1970s, when research in recombinant DNA techniques was halted while a committee of scientists and non-scientists could establish a set of guidelines for conducting the work safely. Falkow argues that research on H5N1 viruses with enhanced transmissibility should move forward once scientists work with the public to establish standardized guidelines using common sense and scientific creativity.

“This is a historic time in science,” says Casadevall. mBio® has solicited the views of experts in the field, he says, in order to provide a venue for recording the arguments for and against continuing H5N1 gain-of-function research. “Society is asking for a pause of research that is perhaps the best defense against pandemics because of concern about both biosafety and biosecurity.” With the research moratorium continuing well past the 60-days originally planned, it is time these conflicting views were aired in a public forum, he says.

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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 at http://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

UCLA/Pitt scientists uncover virus with potential to stop pimples in their tracks

Contact: Elaine Schmidt eschmidt@mednet.ucla.edu 310-794-2272 University of California – Los Angeles Health Sciences

Going viral to kill zits

Watch out, acne.  Doctors soon may have a new weapon against zits:  a harmless virus living on our skin that naturally seeks out and kills the bacteria that cause pimples.

The Sept. 25 online edition of the American Society for Microbiology’s mBio publishes the findings by scientists at UCLA and the University of Pittsburgh.

“Acne affects millions of people, yet we have few treatments that are both safe and effective,” said principal investigator Dr. Robert Modlin, chief of dermatology and professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.  “Harnessing a virus that naturally preys on the bacteria that causes pimples could offer a promising new tool against the physical and emotional scars of severe acne.”

The scientists looked at two little microbes that share a big name:  Propionibacterium acnes, a bacterium thriving in our pores that can trigger acne; and P. acnes phages, a family of viruses that live on human skin.  The viruses are harmless to humans, but programmed to infect and kill the aforementioned P. acnes bacteria.

When P. acnes bacteria aggravate the immune system, it causes the swollen, red bumps associated with acne.  Most effective treatments work by reducing the number of P. acnes bacteria on the skin.

“We know that sex hormones, facial oil and the immune system play a role in causing acne, however, a lot of research implicates P. acnes as an important trigger,” explained first author Laura Marinelli, a UCLA postdoctoral researcher in Modlin’s laboratory.  “Sometimes they set off an inflammatory response that contributes to the development of acne.”

Using over-the-counter pore cleansing strips from the drugstore, the researchers lifted acne bacteria and the P. acnes viruses from the noses of both pimply and clear-skinned volunteers.

When the team sequenced the bacteriophages’ genomes, they discovered that the viruses possess multiple features – such as small size, limited diversity and the broad ability to kill their hosts – that make them ideal candidates for the development of a new anti-acne therapy.

“Our findings provide valuable insights into acne and the bacterium that causes it,” observed corresponding author Graham Hatfull, Eberly Family Professor of Biotechnology, professor of biological sciences at the University of Pittsburgh and a Howard Hughes Medical Institute researcher.  “The lack of genetic diversity among the phages that attack the acne bacterium implies that viral-based strategies may help control this distressing skin disorder.”

“Phages are programmed to target and kill specific bacteria, so P. acnes phages will attack only P. acnes bacteria, but not others like E. coli,” added Marinelli.  “This trait suggests that they offer strong potential for targeted therapeutic use.”

Acne affects nearly 90 percent of Americans at some point in their lives, yet scientists know little about what causes the disorder and have made narrow progress in developing new strategies for treating it.  Dermatologists’ arsenal of anti-acne tools — benzoyl peroxide, antibiotics and Accutane – hasn’t expanded in decades.

“Antibiotics such as tetracycline are so widely used that many acne strains have developed resistance, and drugs like Accutane, while effective, can produce risky side effects, limiting their use,” explained coauthor Dr. Jenny Kim, director of the UCLA Clinic for Acne, Rosacea and Aesthetics.  “Acne can dramatically disfigure people and undermine their self-esteem, especially in teens.  We can change patients’ lives with treatment.  It’s time we identified a new way to safely treat the common disorder.”

The research team plans to isolate the active protein from the P. acnes virus and test whether it is as effective as the whole virus in killing acne bacteria. If laboratory testing proves successful, the researchers will study the compound’s safety and effectiveness in combating acne in people.

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The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR060382, R01 AR053542 and F32AR060655) at the National Institutes of Health in Bethesda, Md.

Additional coauthors included Sorel Fitz-Gibbon, Megan Inkeles, Shawn Cokus, Matteo Pellegrini and Jeffrey F. Miller, all of UCLA; former UCLA researchers Clarmyra Hayes and Anya Loncaric, now of the California Institute of Technology and Solta Medical, respectively; and  Charles Bowman, Daniel Russell and Deborah Jacobs-Sera of the University of Pittsburgh.

The Clinic for Acne, Rosacea and Aesthetics at the UCLA Division of Dermatology at the David Geffen School of Medicine offers comprehensive care for acne and rosacea, as well as the scarring and discoloration that can result from these conditions.  The clinic’s goal is to educate the public and help patients develop habits leading to healthy skin.  Current research projects include studying the effect of Vitamin-D on immune response to acne, the effect of Omega-3 fatty acids on acne and its treatment, and the use of a mobile device application for acne management.  To schedule an appointment, call (310) 825-6911

Pathogen that causes disease in cattle also associated with Crohn’s disease: Mycobacterium avium paratuberculosis

For File 2008

Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology

Research urgently needed to evaluate potential risks to humans

People with Crohn’s disease (CD) are seven-fold more likely to have in their gut tissues the bacterium that causes a digestive-tract disease in cattle called Johne’s disease. The role this bacterium may or may not play in causing CD is a top research priority, according to a new report released by the American Academy of Microbiology. The reports points out that the cause of CD is unknown, and the possible role of this bacterium—which could conceivably be passed up the food chain to people—has received too little attention from the research community.

The report, Mycobacterium avium paratuberculosis: Incidental Human Pathogen or Public Health Threat?, summarizes conclusions and recommendations from a colloquium convened by the American Academy of Microbiology in June 2007 that brought together experts in microbiology, medicine, veterinary pathology, epidemiology, infectious diseases, and food safety. Colloquium participants described the state of knowledge about the relationship between Mycobacterium avium subspecies paratuberculosis (MAP) and CD and developed a research agenda to move the field forward.

Scientists largely agree that multiple factors cause CD, including an environmental stimulus, a genetic propensity, and an overactive inflammatory and immune system triggered by an unknown event. There is mounting evidence that the unknown trigger may be infectious in origin, with several bacteria currently under consideration. “This complicated network of causation has confounded efforts to understand CD, says Carol Nacy, Ph.D., CEO of Sequella, Inc., who chaired the colloquium and is the report’s co-author. “MAP may be one of the causes of CD,” Nacy adds, “since, among other things, multiple studies identified the pathogen in tissues of CD patients. Treating some of these patients with antibiotics that target Mycobacteria provided relief from symptoms.”

Johne’s disease is a severe and fatal bacterial infection that strikes cattle, sheep, and other livestock. MAP has long been identified as the cause of Johne’s disease. Despite efforts to limit the spread of MAP, roughly 68% of cattle herds in this country are infected, meaning one or more animals in the herd carry the bacterium and may develop Johne’s disease or spread the infection to other animals. MAP has been found in some dairy products—milk and cheese—and beef on supermarket shelves.

The critical steps for research now, according to the report, are to determine whether humans are exposed and infected with MAP by eating infected meat and dairy products and whether MAP causes or incites CD or whether it is only incidentally present in those afflicted with the disease. The prospect that MAP could play a role in the incitement or development of CD is a sobering one, and, once the situation becomes clearer through research, there could be important changes in store for agriculture, food safety, and public health. It is in the best interest of the public that the possible connection between MAP and CD be explored exhaustively, according to the report.

The research agenda, however, is seriously hampered by the lack of reliable methods for isolating and indentifying MAP and for diagnosing people with MAP infection. Public health laboratories and U.S. Centers for Disease Control and Prevention laboratories have made it clear they cannot grow MAP in the laboratory—an inability that hinders diagnosis and screening. The report recommends establishment of a task force to develop a specific road map for improved methods for MAP detection and diagnosis.

 

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A full copy of the report and further recommendations can be found on the Academy website at www.asm.org/colloquia/ext.

The American Academy of Microbiology is the honorific leadership group of the American Society of Microbiology. The mission of the Academy is to recognize scientific excellence, as well as foster knowledge and understanding in the microbiological sciences. For more information about the American Society for Microbiology, contact Barbara Hyde at 202-942-9206 or visit www.asm.org.

Pneumococcal disease rates down significantly post-vaccine: But One of the non-vaccine strains, 19A showed an increase of 264%

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Pneumococcal disease rates down significantly post-vaccine

Since the approval of a vaccine against pneumococcal bacteria for young children in 2000, rates of invasive pneumococcal disease (IPD) are down significantly in all age groups, while rates of IPD caused by non-vaccine strains are modestly on the rise.  Researchers from the Centers for Disease Control and Prevention (CDC) report their results today (March 18) at the 2008 International Conference on Emerging Infectious Diseases in Atlanta, Georgia.

“This vaccine is continuing to provide a very substantial public health impact 6 years after its introduction.  We estimate that between 2001 and 2006, 170,000 cases and 9,800 deaths were prevented as a result of this vaccine,” says Matthew Moore of the CDC, a lead researcher on the study.

Streptococcus pneumoniae, also called pneumococcus, is one of the most common causes of bacterial pneumonia and deadly bloodstream infections in the United States. It can also cause bacterial meningitis in children and adults.  In its less severe forms it commonly causes ear infections.  Pneumococcus bacteria can be found colonizing many people’s noses without causing infection.  Why it suddenly invades the body and causes disease is unknown.

A vaccine against pneumococcal disease has been available for adults and children over 2 years of age since the 1980s, but in 2000 a new vaccine, known as PCV7, was approved by the FDA for children under 5 years of age.

The CDC has been tracking the incidence of IPD, the most severe form of the disease – defined as meningitis or a bloodstream infection, which can include some cases of pneumonia – since the introduction of the vaccine.  Moore and his colleagues compared rates of IPD in 2006 with reported rates for 1998-1999, just before PCV7 was introduced.

The researchers found a significant decline in IPD rates for all age groups (-78%, under 5 years; -38%, 5-17 years; -39%, 18-49 years; -14%, 50-64 years; -32%, 65-79 years; and -42%, 80 years and older) with even greater declines in IPD caused by those strains included in the PCV7 vaccine.  The incidence of IPD caused by strains not included in the vaccine rose by 40%.  One of the non-vaccine strains, 19A showed an increase of 264%, but Moore cautions that because these strains were relatively uncommon before the introduction of the vaccine, the increase in actual numbers is still small.

“PCV continues to provide impressive public health benefits after introduction.  Disease caused by non-PCV7 serotypes, especially 19A, is emerging and accounts for nearly all IPD.  Newer conjugate vaccines targeting more serotypes are needed to further reduce IPD,” says Moore.

The introduction of PCV7 may have also helped solve an enduring mystery associated with IPD.  The incidence of the disease is seasonal with rates running 5 times higher in the winter, but there is also a sharp but unexplained spike that occurs annually in older adults during the weeks around January 1.

Nicholas Walter of the CDC and his colleagues analyzed 11 years worth of IPD surveillance data and noticed that after the introduction of PCV7 the spikes were much less severe.  Since PCV7 is used in children, they had to figure that into the equation somehow.  Based on the data, Walter and his colleagues now believe the annual spike may be the result of older adults being exposed to colonized children when families get together for the winter holidays.

“Timing of the spikes and the predominance of older adults suggest the spikes may be related to older adults’ increased exposure to young children around the winter holidays,” says Walter, who also presented his data at the meeting.  The observation that spikes diminished after introduction of PCV7 gives further indication that vaccination of children limits disease not only in children, but also in adults.  Many of these infections may be preventable with pneumococcal polysaccharide vaccine, which targets 23 different serotypes and is recommended for all adults 65 years of age and older.

 

Resposted at Request 2008 Data

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The International Conference on Emerging Infectious Diseases is organized by the Centers for Disease Control and Prevention (CDC), the American Society for Microbiology, the Council of State and Territorial Epidemiologists, the Association of Public Health Laboratories and the World Health Organization.  More information on the meeting can be found online at www.iceid.org.

Bacteria in the gut of autistic children different from non-autistic children

 

The underlying reason autism is often associated with gastrointestinal problems is an unknown, but new results to be published in the online journal mBio® on January 10 reveal that the guts of autistic children differ from other children in at least one important way: many children with autism harbor a type of bacteria in their guts that non-autistic children do not. The study was conducted by Brent Williams and colleagues at the Mailman School of Public Health at Columbia University.

Earlier work has revealed that autistic individuals with gastrointestinal symptoms often exhibit inflammation and other abnormalities in their upper and lower intestinal tracts. However, scientists do not know what causes the inflammation or how the condition relates to the developmental disorders that characterize autism. The research results appearing in mBio® indicate the communities of microorganisms that reside in the gut of autistic children with gastrointestinal problems are different than the communities of non-autistic children. Whether or not these differences are a cause or effect of autism remains to be seen.

“The relationship between different microorganisms and the host and the outcomes for disease and development is an exciting issue,” says Christine A. Biron, the Brintzenhoff Professor of Medical Science at Brown University and editor of the study. “This paper is important because it starts to advance the question of how the resident microbes interact with a disorder that is poorly understood.”

Bacteria belonging to the group Sutterella represented a relatively large proportion of the microorganisms found in 12 of 23 tissue samples from the guts of autistic children, but these organisms were not detected in any samples from non-autistic children. Why this organism is present only in autistic kids with gastrointestinal problems and not in unaffected kids is unclear.

Sutterella has been associated with gastrointestinal diseases below the diaphragm, and whether it’s a pathogen or not is still not clear,” explains Jorge Benach, Chairman of the Department of Microbiology at Stony Brook University and a reviewer of the report. “It is not a very well-known bacterium.”

In children with autism, digestive problems can be quite serious and can contribute to behavioral problems, making it difficult for doctors and therapists to help their patients. Autism, itself, is poorly understood, but the frequent linkage between this set of developmental disorders and problems in the gut is even less so.

Benach says the study was uniquely powerful because they used tissue samples from the guts of patients. “Most work that has been done linking the gut microbiome with autism has been done with stool samples,” says Benach, but the microorganisms shed in stool don’t necessarily represent the microbes that line the intestinal wall. “What may show up in a stool sample may be different from what is directly attached to the tissue,” he says.

Tissue biopsy samples require surgery to acquire and represent a difficult process for the patient, facts that underscore the seriousness of the gastrointestinal problems many autistic children and their families must cope with.

Benach emphasizes that the study is statistically powerful, but future work is needed to determine what role Sutterella plays, if any, in the problems in the gut. “It is an observation that needs to be followed through,” says Benach.

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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 at http://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