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  • richardmitnick 1:58 pm on July 20, 2017 Permalink | Reply
    Tags: , , , Methicillin, MRSA, St. Andrews, The mecA gene confers resistance by producing a protein called PBP2a   

    From St. Andrews: “MRSA emerged years before methicillin was even discovered” 

    U St Andrews bloc

    University of St Andrews

    20 July 2017
    Christine Tudhope
    01334 467 320
    07526 624 243 or
    christine.tudhope@st-andrews.ac.uk

    1
    No image caption or credit

    Methicillin resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to researchers at the University of St Andrews.

    A new study, in collaboration with the Wellcome Trust Sanger Institute and the University of Dundee, suggests the widespread use of earlier antibiotics such as penicillin rather than of methicillin itself allowed Methicillin resistant Staphylococcus aureus (MRSA) to emerge.

    The findings, published in the open access journal Genome Biology, found that S. aureus acquired the gene that confers methicillin resistance (mecA) as early as the mid-1940s, fourteen years before the first use of methicillin.

    Professor Matthew Holden, molecular microbiologist at the University of St Andrews, the corresponding author said:

    “Our study provides important lessons for future efforts to combat antibiotic resistance. It shows that new drugs which are introduced to circumvent known resistance mechanisms, as methicillin was in 1959, can be rendered ineffective by unrecognized, pre-existing adaptations in the bacterial population. These adaptations happen because, in response to exposure to earlier antibiotics, resistant bacterial strains are selected instead of non-resistant ones as bacteria evolve.”

    The mecA gene confers resistance by producing a protein called PBP2a, which decreases the binding efficiency of antibiotics used against S. aureus to the bacterial cell wall. The introduction of penicillin in the 1940s led to the selection of S. aureus strains that carried the methicillin resistance gene.

    Dr Catriona Harkins, clinical lecturer in dermatology at the University of Dundee, the first author of the study said:

    “Within a year of methicillin being first introduced to circumvent penicillin resistance, strains of S. aureus were found that were already resistant to methicillin. In the years that followed resistance spread rapidly in and outside of the UK. Five decades on from the appearance of the first MRSA, multiple MRSA lineages have emerged which have acquired different variants of the resistance gene.”

    To uncover the origins of the very first MRSA and to trace its evolutionary history, the researchers sequenced the genomes of a unique collection of 209 historic S. aureus isolates. The oldest of these isolates were identified over 50 years ago by the S. aureus reference laboratory of Public Health England and have been stored ever since in their original freeze-dried state. The researchers also found genes in these isolates that confer resistance to numerous other antibiotics, as well as genes associated with decreased susceptibility to disinfectants.

    Professor Holden said:

    “S. aureus has proven to be particularly adept at developing resistance in the face of new antibiotic challenges, rendering many antibiotics ineffective. This remains one of the many challenges in tackling the growing problem of antimicrobial resistance. In order to ensure that future antibiotics retain their effectiveness for as long as possible, it is essential that effective surveillance mechanisms are combined with the use of genome sequencing to scan for the emergence and spread of resistance.”

    Science paper:
    Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice.

    See the full article here .

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    U St Andrews campus

    St Andrews is made up from a variety of institutions, including three constituent colleges (United College, St Mary’s College, and St Leonard’s College) and 18 academic schools organised into four faculties. The university occupies historic and modern buildings located throughout the town. The academic year is divided into two terms, Martinmas and Candlemas. In term time, over one-third of the town’s population is either a staff member or student of the university. The student body is notably diverse: over 120 nationalities are represented with over 45% of its intake from countries outside the UK; about one-eighth of the students are from the rest of the EU and the remaining third are from overseas — 15% from North America alone. The university’s sport teams compete in BUCS competitions, and the student body is known for preserving ancient traditions such as Raisin Weekend, May Dip, and the wearing of distinctive academic dress.

     
  • richardmitnick 7:49 am on August 17, 2016 Permalink | Reply
    Tags: , , Flu and superbug combo causes fatal lung damage, , MRSA   

    From COSMOS: “Flu and superbug combo causes fatal lung damage” 

    Cosmos Magazine bloc

    COSMOS

    17 August 2016
    Amy Middleton

    The virus causes white blood cells to attack lungs, inflaming the tissue and giving MRSA an easier infection route.

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    As if having the flu wasn’t bad enough – the virus increases susceptibility to secondary bacterial infections by turning your own immune cells against your lungs. Lester V. Bergman / Getty Images

    A golden staph infection during or after catching the flu ends up killing more patients because the virus urges white blood cells to attack patients’ lungs, a new study claims.

    The work, which traced how the virus and bacteria act in mice, was published in the Journal of Experimental Medicine.

    Strains of golden staph (Staphylococcus aureus) have developed immunity to commonly used antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is one such superbug.

    When patients are infected with influenza – a virus – they’re more susceptible to bacterial infection. But post-influenza patients that contract MRSA can end up with severe cases of S. aureus pneumonia.

    In more than half these cases, the patient will die, even if they take a course of antibiotics that usually win out against MRSA.

    The reason antibiotics are ineffective, according to researchers led by Keer Sun at the University of Nebraska in the US, is the patient’s wayward white blood cells.

    Sun and colleagues examined how flu infection tinkers with macrophages and neutrophils, two types of white blood cell that usually mobilise against infections.

    In normal cases, these cells release atoms or molecules called reactive oxygen species that help to destroy pathogens. But when a patient is infected with influenza, this process is altered – the white blood cells end up targeting cells in the lung area, causing inflammation and damage to the surrounding tissue that can give MRSA an easy infection route.

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    The lungs of mice co-infected with influenza and MRSA appear much healthier after combined treatment with antibiotics and a Nox2 inhibitor (right) than they do after antibiotic treatment alone (left). Sun et al., 2016

    According to studies on flu-infected mice, stopping white blood cells from releasing of NADPH oxidase 2 (Nox2), the enzyme that produces reactive oxygen species in macrophages and neutrophils, can reverse this potentially lethal effect.

    “Our results demonstrate that influenza infection disrupts the delicate balance between Nox2-dependent antibacterial immunity and inflammation,” the researchers write.

    “Treatment strategies that target both bacteria and oxidative stress will significantly benefit patients with influenza-complicated S. aureus pneumonia.”

    See the full article here .

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  • richardmitnick 2:38 pm on November 9, 2015 Permalink | Reply
    Tags: , , , MRSA   

    From Brown: “After beating it, student gymnast takes fight to MRSA with research” 

    Brown University
    Brown University

    November 9, 2015
    David Orenstein

    1

    Athletes are at elevated risk.Having beaten the “superbug,” Tori Kinamon now has methicillin-resistant Staphylococcus aureus squarely in her sights. She hopes her research will lead to strategies for reducing the risk of infection. Photos: Stew Milne for Brown University

    Toward the end of her month-long stay in Rhode Island Hospital, as she began to recover from eight surgeries on her left leg in two weeks, Tori Kinamon of Peachtree City, Ga., was up on crutches, trying out a stairwell where a window faced northeast.

    “I remember looking out and seeing the Sci Li across the way and the reality of my experience really hit me at that moment,” she said. “I remember thinking, ‘That’s where I should be right now. I should be in the Sci Li studying or just be on Brown’s campus and instead I’m here.’ That was a really hard reality to face.”

    This was not the way Kinamon wanted to spend the early spring of her freshman year in 2014. Instead of finishing her first season with the Brown gymnastics team and continuing her studies, she was battling an overwhelmingly painful infection of methicillin-resistant Staphylococcus aureus [MRSA]. At its peak the infection seriously threatened to take her leg, if not her life.

    In the end, the so-called “superbug” took a lot of muscle and left a two-foot long scar, but last spring Kinamon was back up on the uneven bars in competition for her team and her school. She had made the decision that MRSA wasn’t going to chase her out of the gym. Gymnastics is the closest thing to flying, she said, and after competing as an individual throughout high school she was indelibly excited to be part of a team at Brown.

    Kinamon managed to finish her freshman year courses from home early that summer, but it would take much longer to rebuild the lost muscle to competition strength. She had a lingering fear that somehow she could become infected again, but she had the drive, the faith, and the support of her team and family to fly again.

    “I didn’t just want to be able to walk, I wanted to be able to run and jump and return to my previous fitness level,” she said. “I didn’t want the MRSA infection to define what I did.”

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    A broader perspective “It’s enabled me to explore how I can translate my experience into something that helps others avoid this preventable infection.

    In the best way, though, that’s only half-true. While she has defied MRSA by competing again athletically (winning the Mari-Rae Sopper Spirit Award from USA Gymnastics in April), she has made MRSA a defining aspect of her academic life. She didn’t just fend off the bacterium. As a Brown student, she’s now coming after it.

    Resurgent with research

    This semester the health and human biology concentrator is taking classes on the epidemiology of infectious diseases, immunology, and the burden of disease in developing nations. But all year she’ll also be working in the lab of Dr. Eleftherios Mylonakis, the Dean’s Professor of Medical Science and chief of infectious diseases at Rhode Island Hospital and The Miriam Hospital.

    Her focus is on finding out how to prevent MRSA from spreading. A lot of research has explored control within hospitals, but far less can explain how it manages to afflict healthy people in the community. Athletes are at elevated risk. Last month, MRSA ended the football season for New York Giants tight end Daniel Fells.

    As in Fells’ case, Kinamon doesn’t know how she got the terrible bacteria, but she wants to find out. She started her research this fall by undertaking a detailed review of the scientific literature on MRSA cases in athletes. She’s studying prevention practices, such as screenings, and information on how infections occur.

    “Right now I’m looking at the prevalence of MRSA colonization in athletes to see if it is known, and if it is known, how do we go about decolonizing people to reduce the risk of transmission to others in the community,” she said. “I hope that will extend to some lab work in looking at specifics of the [particularly virulent] community-acquired MRSA strains.”

    Mylonakis praised Kinamon as “analytical, supremely motivated, meticulous and scientifically curious.” Her personal story has been inspiring for his research group, he said, and her work will add to the scope of what it can accomplish.

    “This work will highlight that everyone — even young individuals at the best shape of their lives — is potentially vulnerable to these resistant pathogens and has already generated scientific questions on the molecular pathogenesis of MRSA that Tori is planning to investigate in the lab,” he said. “Her work has summarized what we know about the spread of MRSA among athletes. More importantly, it demonstrates a lot of missing links that will need to be studied. I anticipate that Tori’s work will be instrumental in developing prophylaxis strategies among athletes.”

    A patient’s perspective

    Doing all this in her junior year gives Kinamon an opportunity to explore more about infectious disease overseas next year. Originally she came to Brown hoping to prepare for medical school with a focus on sports medicine. That remains an interest, but after her ordeal she’s broadened her perspective to pursue a concentration subfocus in global and international health. She’s had the guidance of professors such as Mylonakis, Dr. Tim Flanigan, professor of medicine, and Katherine Smith, associate dean of biology for undergraduate education, but she also took to heart what someone said, perhaps off-handedly, while she was in the hospital.

    “Someone said to me, ‘You’re really lucky you are not in a Third-World country,’” she said. “That made me very interested in why, if someone had a MRSA infection in another country, their outcome could have been totally different just based on the resources they have.”

    Kinamon said being a patient, and not just a student, has changed how she looks at her studies and her future career.

    “When I was hospitalized, my eyes were suddenly and unexpectedly opened to the patient aspect of medicine,” she said. “The experience has allowed me to empathize with people in ways that I couldn’t have before.”

    As much pain and fear as she felt, as hard as she’s had to work, she has come through it with sense of what she gained, rather than what she lost.

    “Looking back on my experience, I wouldn’t change what happened to me because it’s completely altered the way I look not only at the world but also at myself,” she said. “Through Brown’s open curriculum and the breadth of opportunities available, I’ve been able to tailor my educational experience so that I can really look into what happened to me and why it happened. More importantly, it’s enabled me to explore how I can translate my experience into something that helps others avoid this preventable infection.”

    She wouldn’t change her experience, but she might change the game, squashing a superbug as she sticks what once may have seemed to be an impossible landing.

    See the full article here .

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    Welcome to Brown

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    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

     
  • richardmitnick 2:48 pm on September 14, 2015 Permalink | Reply
    Tags: , , MRSA, Staph infection,   

    From Wash U: “Combo of 3 antibiotics can kill deadly staph infections​​​” 

    Wash U Bloc

    Washington University in St.Louis

    September 14, 2015
    Jim Dryden

    1
    Using three antibiotic drugs thought to be useless against MRSA infection — piperacillin and tazobactam (bottle on left) and meropenem — Washington University researchers, led by Gautam Dantas, PhD, have killed the deadly staph infection in culture and in laboratory mice.
    Robert Boston

    2
    Scanning electron micrograph of a human neutrophil ingesting MRSA

    Three antibiotics that, individually, are not effective against a drug-resistant staph infection can kill the deadly pathogen when combined as a trio, according to new research.

    The researchers, at Washington University School of Medicine in St. Louis, have killed the bug — <a href="http://“>methicillin-resistant Staphylococcus aureus (MRSA) — in test tubes and laboratory mice, and believe the same three-drug strategy may work in people.

    “MRSA infections kill 11,000 people each year in the United States, and the pathogen is considered one of the world’s worst drug-resistant microbes,” said principal investigator Gautam Dantas, PhD, an associate professor of pathology and immunology. “Using the drug combination to treat people has the potential to begin quickly because all three antibiotics are approved by the FDA.”

    The study is published online Sept. 14 in the journal Nature Chemical Biology.

    The three drugs — meropenem, piperacillin and tazobactam — are from a class of antibiotics called beta-lactams that has not been effective against MRSA for decades.​​​​​​​​​​​​​​

    2
    Shown are clumps of MRSA bacteria magnified more than 2,300 times by an electron microscope.

    Working with collaborators in the microbiology laboratory at Barnes-Jewish Hospital​ in St. Louis, Dantas’ team tested and genetically analyzed 73 different variants of the MRSA microbe to represent a range of hospital-acquired and community-acquired forms of the pathogen. The researchers treated the various MRSA bugs with the three-drug combination and found that the treatments worked in every case.

    Then, in experiments conducted by collaborators at the University of Notre Dame, the team found that the drug combination cured MRSA-infected mice and was as effective against the pathogen as one of the strongest antibiotics on the market.

    “Without treatment, these MRSA-infected mice tend to live less than a day, but the three-drug combination cured the mice,” Dantas said. “After the treatment, the mice were thriving.”

    Dantas explained that the drugs, which attack the cell wall of bacteria, work in a synergistic manner, meaning they are more effective combined than each alone.

    The researchers also found that the drugs didn’t produce resistance in MRSA bacteria — an important finding since more and more bacteria are developing resistance to available drugs.

    “This three-drug combination appears to prevent MRSA from becoming resistant to it,” Dantas said. “We know all bacteria eventually develop resistance to antibiotics, but this trio buys us some time, potentially a significant amount of time.”

    Dantas’ team also is investigating other antibiotics thought to be ineffective against various bacterial pathogens to see if they, too, may work if used in combination with other drugs.

    “We started with MRSA because it’s such a difficult bug to treat,” he said. “But we are optimistic the same type of approach may work against other deadly pathogens, such as Pseudomonas and certain virulent forms of E. coli.”

    Funding for this research comes from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH). Additional funding comes from an NIH Director’s New Innovator Award and a Ruth Kirschstein National Research Service Award from NIH.

    See the full article here .

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    Washington University’s mission is to discover and disseminate knowledge, and protect the freedom of inquiry through research, teaching, and learning.

    Washington University creates an environment to encourage and support an ethos of wide-ranging exploration. Washington University’s faculty and staff strive to enhance the lives and livelihoods of students, the people of the greater St. Louis community, the country, and the world.

     
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