Bio firm finds structure...of superbug enzyme

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Dec 9, 2008
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A Korean firm said Monday it has identified the structure of a key protein that makes bacteria resistant to nearly all known antibiotics, paving the way for a treatment of the so-called superbug.

Researchers at Crystalgenomics Inc., a Seoul based bio-venture, have succeeded for the first time to find the shape of the New Delhi metallo-beta-lactamase, or NMD-1 enzyme that deactivates antibiotics.

Since its first detection in 2008, the NDM-1 superbug and its variants have been spreading fast across the world.
Crystalgenomics said that its findings have been registered with the Protein Data Bank of the U.S. and that it has filed for an international patent.

The company is now negotiating with several multinational pharmaceutical firms about developing treatments against bacteria that produce the NDM-1 enzyme.

NMD-1 is an enzyme that breaks down carbapenem antibiotics, which are used to treat patients infected by bacteria that are resistant to other beta-lactam antibiotics such as penicillin.

The protein was discovered in August 2010. The World Health Organization in the same month warned it poses a global health problem that could affect the control of diseases such as respiratory infections and dysentery.

The gene for the protein is thought to have originated in India and infection by that strain of bacteria was first described in 2008.

Bacteria infections with the NDM-1 protein have been found in about 22 nations including Australia, Canada and the United Kingdom.

As of December, South Korea had four patients who were confirmed to have been infected with NDM-1 bacteria.

Crystalgenomics is currently testing an antibiotic for another super-bacteria, Methicillin-resistant Staphylococcus aureus or MRSA
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It sounds good!!!
 
Family tree stops MRSA outbreak...
:clap2:
DNA sequencing of MRSA used to stop outbreak
13 November 2012 - An outbreak of the hospital superbug MRSA has been brought to an end by UK doctors cracking the bacterium's genetic code.
It led to them finding one member of staff at Rosie Hospital, in Cambridge, who may have unwittingly carried and spread the infection. They say it is the first time rapid genetic testing has been used to track and then stop an outbreak. One expert said this would soon become "standard practice" in hospitals. Doctors were concerned after MRSA was detected in 12 babies during routing screening. However, current tests could not tell if it was one single outbreak being spread around the unit or if they were separate cases being brought into the hospital. About one in 100 people carry MRSA on their skin without any health problems. To find out, researchers at the University of Cambridge and the Sanger Institute embarked on more sophisticated version of a paternity test. They compared the entire genetic code of MRSA bugs from each baby to build a family tree. It showed they were all closely related and part of the same outbreak.

After two months without a case and deep cleaning the ward, another case appeared. Analysing the DNA showed that it was again part of the outbreak and attention turned to a carrier. Tests on 154 members of staff showed that one was also carrying MRSA, which may have been spread to babies in the unit. They were treated to remove the infection. "We believe this brought the outbreak to a close," said Dr Julian Parkhill, from the Sanger Institute. "This is really exciting for us because it gave the hospital the opportunity to intervene. "We think this is the first case where whole genome sequencing has actually led to a clinical intervention and brought the outbreak to a close." The study was published in the medical journal Lancet Infectious Diseases.

Cheaper

The cost of working out the entire genetic code of a bacterium has plummeted from millions of pounds to about £50. The time it takes has also fallen dramatically from months to hours. Dr Parkhill said it could get even cheaper: "People are talking about the thousand dollar human genome. "If you can do the human genome for a thousand dollars you can do a bacterial genome for one dollar." Commenting on the research Prof Ross Fitzgerald, from the Roslin Institute at the University of Edinburgh, told the BBC: "The study clearly highlights the power of whole genome sequencing for resolving the source and the spread of an epidemic of hospital acquired infection such as MRSA. "It will ultimately, within a small number of years, be standard practice for any hospital outbreak. "I fully expect this to be rolled out as a standard approach in UK hospitals in the very near future."

Prof Sharon Peacock, from the University of Cambridge, said she wanted to develop a simple system that could be used easily by hospitals. She said she envisioned a "black box" where the genetic sequence goes in and a simple report that can be used by hospital staff comes out. "It could, for example, determine the species of the bacterium; it could determine antibiotic susceptibility, and it could provide information about what genes are present that are often associated with poor outcomes in patients." Sir Mark Walport, director of the Wellcome Trust, said: "This is a dramatic demonstration that medical genomics is no longer a technology of the future - it is a technology of the here and now."

BBC News - DNA sequencing of MRSA used to stop outbreak
 
Rising antibiotic resistance...
:eusa_eh:
Antibiotic resistance 'big threat to health'
16 November 2012 - Antibiotic resistance is growing
Resistance to antibiotics is one of the greatest threats to modern health, experts say. The warning from England's chief medical officer and the Health Protection Agency comes amid reports of growing problems with resistant strains of bugs such as E. coli and gonorrhoea. They said many antibiotics were being used unnecessarily for mild infections, helping to create resistance. And they urged patients to take more care with how they used medicines. This is particularly important as there are very few new antibiotics in development.

'Alarming'

The chief medical officer, Prof Dame Sally Davies, said: "Antibiotics are losing their effectiveness at a rate that is both alarming and irreversible - similar to global warming. "I urge patients and prescribers to think about the drugs they are requesting and dispensing. "Bacteria are adapting and finding ways to survive the effects of antibiotics, ultimately becoming resistant so they no longer work. "The more you use an antibiotic, the more bacteria become resistant to it." To reinforce her message, Dame Sally has issued a list of "dos and don'ts". These include:

* Do remember antibiotics should be taken only when prescribed by a health professional.
* Do complete the prescribed course even if you feel better, as not taking the full course encourages the emergence of resistance.
* Don't share antibiotics with anyone else.
* Do remember that antibiotics cannot help you recover from infections caused by viruses, such as colds or flu.

The HPA said the last point was one of the common misconceptions among the public. Dr Cliodna McNulty from the HPA said: "We all seem to forget just how awful you can feel with a bad cold, let alone flu, and this maybe makes us think that we are more poorly than we really are and that we need antibiotics to get better. "But this isn't the case and using your favourite over-the-counter medicines that can help to ease headaches, aching muscles and stop your nose running will make you feel a lot better."

Source
 
Making superbugs vulnerable to existing antibiotics...
:cool:
Scientists Find New Strategy Against Drug-Resistant Superbugs
February 07, 2013 - Scientists may have found an effective new weapon against antibiotic-resistant bacteria. They did not create a new drug to kill these microbes; instead, they found a way to interfere with the metabolism of the extra-hardy bacterium - E. coli in this case - so that the germs became more vulnerable to existing antibiotics.
Scientists believe they have discovered the so-called superbugs’ Achilles heel, a biochemical weakness in the bacteria that makes it possible - in effect - to "kick them while they are down.” Researchers, led by Jim Collins of Harvard's Wyss Institute for Biotechnology in Massachusetts, altered the E. coli's bacterium’s metabolic processes, interfering with its normal production of waste products called ROS, short for "reactive oxygen species."

Normally, the E. coli bacterium would be able to break down the ROS they produce. But Collins, also a professor of biomedical engineering at Boston University, says that by tweaking a number of genes to increase ROS production, scientists forced waste levels within the cell to become destructive, weakening the superbugs and making them vulnerable to antibiotics. Researchers used a computer model to map out the metabolic activity of the E. coli bacterium, selectively deleting genes to see which ones might be involved in increasing the production of ROS, and then zeroing in on the most likely ROS genes.

After switching off these ROS genes and successfully increasing the bacterium's waste production, Collins says scientists conducted experiments with a drug-resistant strain of E. coli, targeting certain areas in the bacterium with standard antibiotics and bleach. “And in each case, we found the targets could boost the killing efficacy from tenfold to a thousand fold," said Collins.

Collins says his team's approach actually mimics how some antibiotics are believed to kill bacteria. He cautions that the new strategy is not a “magic bullet” that can solve the growing problem of antibiotic-resistant bacteria -- a problem that is undermining traditional treatment strategies against lethal diseases such as tuberculosis and pneumonia. But Collins believes the discovery could strengthen our existing arsenal of drugs. “Where this can help address the problem of growing antibiotic resistance is that we’re, with this approach, serving to boost the effectiveness of our existing antibiotics. And we have preliminary data that indicate that this approach can serve to resensitize resistant strains to antibiotics to which they’ve grown resistant," he said.

In other words, there could soon be a pill that would cause drug-resistant bacteria to lose their resistance and allow potentially life-threatening infections to respond to standard antibiotic treatment. An article describing a new method for fighting antibiotic-resistant microbes is published in the journal Nature Biotechnology.

Source
 
Granny says it's dat endtime plague inna Bible - we all gonna die...
:eek:
Officials alarmed by increasing superbug reports
5 Mar.`13 — Health officials say there's been an alarming increase in some dangerous superbugs at U.S. hospitals.
These superbugs are common germs that have become extremely resistant to treatment with antibiotics. The number of hospitals reporting infections with these superbugs is still small. But a government report shows 1 in 25 hospitals saw at least one case last year.

The Centers for Disease Control and Prevention released the new tally Tuesday. They're urging hospital workers to take steps to keep the germs from spreading.

The dangerous germs can cause pneumonia and urinary tract and bloodstream infections in vulnerable, hospitalized patients.

Officials alarmed by increasing superbug reports - Yahoo! News
 
Growing superbug threat to hospitals & nursing homes...
:eek:
CDC says ‘nightmare bacteria’ a growing threat
March 5,`13 - Federal officials warned Tuesday that “nightmare bacteria” — including the deadly superbug that struck a National Institutes of Health facility two years ago — are increasingly resistant to even the strongest antibiotics, posing a growing threat to hospitals and nursing homes nationwide.
Thomas Frieden, director of the Centers for Disease Control and Prevention, said at a news conference: “It’s not often that our scientists come to me and say we have a very serious problem and we need to sound an alarm. But that’s exactly what we are doing today.” He called on doctors, hospital leaders and health officials to work together to stop the spread of the infections. “Our strongest antibiotics don’t work, and patients are left with potentially untreatable infections,” he said. Although the bacteria, known as Carbapenen-Resistant Enterobacteriaceae, or CRE, haven’t spread to the wider community — like some other germs — they are more dangerous, said Frieden, who described them as a “triple threat.”

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Deadly "superbugs" -- resistant to even the strongest antibiotics -- have been found in 42 states. Dr. Thomas Frieden, director of the Centers for Disease Control, talks to Charlie Rose and Norah O'Donnell.

First, the bacteria are resistant to all or nearly all antibiotics, even those of last resort, he said. Second, they kill up to half of patients who get bloodstream infections from them. And third, the bacteria can transfer their antibiotic resistance to other bacteria within the family, potentially making other bacteria untreatable, as well. For example, carbapenem-resistant Klebsiella, which caused the NIH outbreak, “can spread the genes that destroy our last antibiotics to other bacteria, such as E. coli, and make E. coli resistant to antibiotics also,” Frieden said. E. coli is the most common cause of urinary tract infections in healthy people.

In 10 years, the percentage of Enterobacteriaceae resistant to antiobiotics increased almost fourfold, to 4.2 percent in 2011 from 1.2 percent in 2001, according to data reported to CDC. And the strain that caused the NIH outbreak has increased sevenfold in the past decade, according to a CDC report issued Tuesday. During the first half of 2012, almost 200 hospitals and long-term acute-care facilities treated at least one patient infected with these bacteria. The CDC did not have statistics for fatalities. Enterobacteriaceae are a family of more than 70 bacteria, including E. coli, that normally live in the digestive system. Over time, some of these bacteria have become resistant to a group of antibiotics known as carbapenems, often referred to as last-resort antibiotics. During the past decade, CDC tracked one type of CRE from a single health-care facility to facilities in at least 42 states, according to a CDC news release.

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Nursing homes on guard for CRE...
:eusa_eh:
Nursing homes brace for the "nightmare bacteria"
March 11, 2013 - Longterm care facilities are bracing for what federal health officials call a "nightmare" drug-resistant bacteria that kills almost half of those it infects, after officials received a strongly worded advisory last week.
A new report showed cases of the bacteria soared five-fold in 10 years and spread from one state to 42. It is believed to have caused 17 South Florida deaths. Dr. Thomas R. Frieden, director of the federal Centers for Disease Control and Prevention, said last week that while CRE cases remain clustered in hospitals and care facilities, healthcare leaders need to "act rapidly" to prevent the bacteria's spread to the community. Frieden said he supports reporting cases in hospitals. The bacteria also has built up defenses against almost all antibiotics, CDC officials said, making it extremely dangerous when it invades the bloodstream.The bacteria typically is spread through contaminated medical equipment such as IV lines, or person-to-person contact.

Just since 2008, health officials have investigated seven Florida outbreaks involving 285 people of carbapenem-resistant Enterobacteriaceae, or CRE. Two were in Broward County, infecting 40 patients and resulting in 17 "associated" deaths, state health officials said. There were no Palm Beach County outbreaks in that time period. "I think this is a serious issue for the state with the highest percentage of elders in the country," said LuMarie Polivka-West, senior vice president of the Florida Health Care Asssociation, which represents most of the state's nursing homes. While she knew of no CRE cases in nursing homes, "we anticipate family members will be concerned." That's because the "superbug," which can thwart even the strongest antibiotics, preys on people who are very elderly or in a weakened condition.

Polivka-West said the association is talking with its members about developing a surveillance system, where nursing homes would report individual cases in order to better track them. Florida, like most states, requires notifications only of "outbreaks," loosely defined as multiple cases that appear in some way connected. Both Broward outbreaks — in 2008 and in 2010-11 — were in long-term acute care hospitals, places for people too sick to be discharged to rehab centers, and who often are on ventilators or catheters. Florida Department of Health spokeswoman Ashley Carr said the facility names are protected under state law.

There are four such hospitals licensed in Broward and Palm Beach counties: Three belong to Louisville-based Kindred Healthcare, and one hospital in Lake Worth to Select Medical, out of Pennsylvania. Representatives from Kindred and Select did not return several phone and email requests for comment Monday. CRE has been around for years and accounted for only about 4 percent of all infections in 2012, according to the federal Centers for Disease Control and Prevention. The report showed long-term acute care hospitals had the highest percentage of cases per number of facilities.

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Granny says, "Dat's right - we all gonna die o' plagues an' pestilences, just like it says inna Bible...

Unchecked superbugs could kill 10 million a year, cost $100 trillion
11 Dec.`14 - Drug-resistant superbugs could kill an extra 10 million people a year and cost up to $100 trillion (£63.68 trillion) by 2050 if their rampant global spread is not halted, according to a British government-commissioned review.
Such infections already kill hundreds of thousands of people a year and the trend is growing, the review said, adding: "The importance of effective antimicrobial drugs cannot be overplayed." Former Goldman Sachs chief economist Jim O'Neill, who led the work, noted that in Europe and the United States alone around 50,000 people currently die each year from infections caused by superbug forms of bacteria such as E.coli. "Unless something is done by 2050, that number could become 10 million people losing their lives each year from then onwards," he told a briefing in London. Antimicrobials are a class of drugs that includes antibiotics, antivirals, antiparasitics and antifungals.

The review of antimicrobial resistance (AMR) is based on analysis by two sets of researchers, RAND and KPMG, estimating the future impact of AMR under different scenarios for six common infections -- three bacterial infections, plus malaria, HIV and tuberculosis. But it excludes indirect effects of growing drug resistance which could "cast medicine back to the dark ages", the review said, by making routine procedures more dangerous. The problem posed by infections developing resistance to such drugs has been a feature of medicine since Alexander Fleming's discovery of the first antibiotic, penicillin, in Britain in 1928.

But it has worsened in recent years as multi-drug-resistant bugs have developed and drug companies have reduced investment in an unprofitable field. The World Health Organization has warned that a post-antibiotic era, where basic healthcare becomes far more dangerous due to risk of infection during routine operations, could arrive this century unless something drastic is done.

O'Neill, who was asked by British Prime Minister David Cameron in July to take a global economist's view of the problem, said he feared the assessment of its $100 trillion impact may be too conservative. "As big as that number might seem, it almost definitely underestimates the true economic cost," he said. O'Neill said this review was the first of several, with more due next year and a final report scheduled for 2016. His team has been asked to set out a plan for accelerating development of new antimicrobial drugs, including antibiotics, and looking into ways of incentivising drugmakers to produce them.

Unchecked superbugs could kill 10 million a year cost 100 trillion - Yahoo News
 
New superbug antibiotic discovered...

New Antibiotic Offers Hope Against Resistant Bugs
January 07, 2015 ~ International public health officials have expressed alarm that once highly-effective antibiotics, developed in some cases more than 50 years ago, are losing the war against dangerous infections, allowing once treatable diseases to grow into deadly illnesses worldwide — so-called "superbugs."
These include the bacterium that causes tuberculosis, which silently infects up to one-third of the world’s population. It can spring to life and cause active disease, and a sometimes fatal skin infection called methicillin-resistant Staphylococcus aureus, or MRSA, that is spread through hospitals, clinics and nursing homes. But a new antibiotic discovered by an international team of researchers is unlikely to fail where other drugs have. Called Teixobactin, it is made by Eleftheria terrae, one of 10,000 previously untested bacterial strains found in soil. The compound is manufactured by the company Novo Biotic.

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Newly discovered bacterium Eleftheria terrae makes an antibiotic that could be a new weapon against resistant infections.

According to Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern University in Boston, Massachusetts, traditional antibiotics, also developed from soil microbes, work by binding to bacterial proteins that are essential for the microbe to thrive. After a while, Lewis says, many bacteria adapt themselves to the drugs and develop avoidance mechanisms. “Mutations occur, the protein changes and the antibiotic no longer binds," said Lewis, lead author of the study describing the new antibiotic compound in the journal Nature. "The targets of teixobactin are not proteins. It hits two different targets. These targets are precursors of cell wall polymers and they do not mutate. There is nothing to mutate. So, at least by that common mechanism, resistance does not occur.” Teixobactin destroys bacteria by causing their cell walls to break down.

The compound was tested in mice infected with three aggressive pathogens — Clostridium difficile, Mycobacterium tuberculous and Staphylococcus aureus — and it cleared the infections. For experts such as Ontario-based Gerry Wright of McMaster University, teixobactin and drugs like it are long overdue. “If you find a new antibiotic, you want to be able to find something that there’s not a lot of existing resistance to, or that resistance will be hard to get," said Wright, who drafted an accompanying analysis of Lewis’s work in Nature. "And so, mission accomplished, in that case. We don’t know if it’s going to be a drug, but [Lewis] is on his way trying to see if it might be.” At the earliest, it’s estimated that teixobactin and drugs in the same class will not become available for at least five years, pending more animal tests and human clinical trials.

New Antibiotic Offers Hope Against Resistant Bugs
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