BREAKING DOWN THE RESISTANCE: By gaining a fuller understanding of how drug-resistant bacteria mutate and are transmitted among individuals, scientists hope to better target prevention methods.
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Resistant strains of the bacteria Staphylococcus aureus are the scourge of hospitals worldwide, frequently sickening and killing patients who were admitted to overcome other ills. And until now, scientists have not been able to closely track the transmission and mutation patterns of single strains.
A new project, using high-throughput, whole-genome sequencing, has begun to demystify MRSA (methicillin-resistant Staphylococcus aureus), revealing how the bacteria tend to spread among patients—and continents. Results of the project were published online January 21 in the journal Science.
The researchers took as their main subject a common strain of the bacteria known as ST239. "We knew that this strain was widespread," said Sharon Peacock, of the Department of Medicine at the University of Cambridge in England, in a conference call with reporters January 20. "But we had no idea how transmission was occurring." Given that MRSA has been found worldwide, scientists assumed it was capable of traveling between continents, but just how and where various subtypes were spreading remained obscured by low-resolution data.
Using older analysis techniques, such as multilocus sequence typing (MLST), most isolates of a MRSA strain appeared to have the same genetic profile. Scientists would typically sample DNA sequences in six or seven genes across the whole MRSA genome (which contains some 3,000 genes). At this rough resolution, subtle genetic changes would often go undetected, the researchers behind the new study explained. More rapid, whole-genome sequencing, however, enabled researcher to see "very precise differences" that occur on the level of single-nucleotide changes, Stephen Bentley, from the Wellcome Trust Sanger Institute (WTSI) in Cambridge, and senior study author, said during the teleconference. For instance, dozens of MRSA isolates collected across the globe (from Asia, Australia, Europe, and North and South America) between 1982 and 2003 had appeared identical using the MLST approach, but with the newer, whole-genome analysis, each proved to be genetically distinct.
The more thorough process, when applied to MRSA, has created "a leap in understanding," which allowed the researchers to construct a rough genetic evolutionary tree for the ST239 strain of MRSA. "It allows us to estimate the date of emergence and trace how it subsequently spread across the world," Simon Harris, also of WTSI, said during the call. This strain in particular appears to have emerged in Europe in the 1960s—a time when antibiotic use was on the rise in that part of the world.
Mutations on the move
In comparing the genetic sequences of the bacteria samples that had been collected on various continents, the team found that the isolates tended to be strongly clustered geographically, with closely related forms throughout South America, whereas others were more common in Asia. This finding "suggests that intercontinental transmission is a rare event," Harris said. The paper describing the project highlights some of these apparently infrequent infections, describing one instance, for example, in which a Brazilian line of MRSA cropped up in a Portugal hospital, showing that the infection does occasionally get transmitted between continents.
All of these conclusions are made possible by the newly detailed picture of the genetic changes that the bacterium undergoes across generations. This process of genetic mutation is occurring at the rate of about one core base pair every six weeks, the researchers deduced. It may sound plodding, but this rate is "far faster than was previously thought," Harris said. This bacterium's substitution rate is, the authors pointed out, about 1,000 times more rapid than the estimated rate for Escherichia coli.
Beyond the speed of mutations, their accumulation seemed to boost the most problematic aspect of the MRSA—its antibiotic resistance. And mutations that provide resistance appear to have happened on multiple occasions in various lines of a single strain, as Harris explained: "Mutations that confer resistance are occurring around the world." In particular, the resistance appears specifically tuned to popular antibiotics, which put "an immense selective pressure" on the bacteria, Harris said. In fact, some 29 percent of convergent mutations "can be directly related to evolution of resistance to antibiotic drugs currently in use, confirming clinical practice as a major driver of pathogen evolution," the researchers concluded in the study.
By studying the origins and transmission patterns of MRSA, researchers hope to be able to recommend more effective ways to stem the spread of this aggressive form of staph—not just within hospitals but also among them and within other settings. With the higher-resolution analysis, "you can see if strains are being transmitted from patient to patient or being brought into the hospital," Peacock said. Highly diverse samples collected over just seven months from a hospital in Thailand indicate that "there [were] multiple introductions," Harris said. At this point it is not clear where these introductions are likely coming from, whether it is from workers, patients or visitors who have picked up the infection in other health care or community settings, but it is clear that the map of transmission has expanded beyond wards and hospital walls.
"We think about MRSA in two distinct boxes: hospital-acquired MRSA and community-acquired MRSA," Peacock said. Increasingly, the two are overlapping, and Peacock noted that the community-acquired side appears to be growing even more prevalent. Although this analysis was conducted on hospital-based cases, an assay could also be done on community-based MRSA, she said.
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14 Comments
Add Commentwhy not program a bacteria to feed on the harmful strain while making sure it itself will not mutate and remain harmless. I know... sci-fi...
Reply | Report Abuse | Link to thisexcellent article....now to just sequence the millions of others...and make use of it.
Reply | Report Abuse | Link to thisPerhaps they could also use this to find a target unique to all strains of staph and then engineer a phage to exploit it.
Reply | Report Abuse | Link to thisI acquired HA-MRSA after an operation. The damage to my inner abdominal lining is unbelievable and probably will be for the years to come. While at my hospital bed side my doctor has said that he himself had MRSA in the past. I not only believe patients but doctors and nurses themselves should be screened for MRSA before operating or being operated on. It's a horrible infection and I'm personally affended when I get a " Oh, it's so common, it's not a big deal " reply when I tell a doctors what I've been thru. Get a grip on something called reality doc's... it is a BIG deal.
Reply | Report Abuse | Link to thisLuckily I had health insurance however I do not believe my insurance company or any insurance company as well as medicaid ie. the citizens of this country should be financially responsible for the recovery costs that are purely the hospitals fault. The hospitals themselves are to blame for recklessly endangering human lives without fully marginal efforts to stop it. America should insist on their liability.
http://www.privatehealth.co.uk/hospitaltreatment/treatment-abroad/mrsa-europe/
Reply | Report Abuse | Link to thishttp://www.politics.ie/health-social-affairs/121500-norway-conquers-mrsa-irish-public-debate-still-misinformed.html
As someone who watched his father suffer and die from MRSA, VRE, and other HAIs, I completely understand the need to place blame for this outrageous and wholly preventable epidemic. Having said that, I think that we need to go beyond blame and focus on what can be done to stop the spread of these lethal bugs in all healthcare institutions. Clearly, healthcare leadership has for decades failed in this regard, despite being aware of the problem and possessing the tools to stop it. This new study adds yet more evidence to an already overwhelming body of science as to the reason for nosocomial spread of MRSA, VRE and other pathogens and what needs to be done to end the destruction. The only question that remains to be answered, in my opinion, is will we continue to be so corrupt and arrogant in insisting that more studies be done, more money allocated to research, and more incentives be given to drug companies to develop new antibiotics, or will we change the culture to focus on prevention by using the cost effective infection control methods that we know work and that have always been available. We have not just a right to ask this, we have an obligation to demand it.
Reply | Report Abuse | Link to thisMichael Bennett
The Coalition For Patients' Rights.
Maybe i am just a tenth grader and yes i didn't even know about this MRSA thing until i read this article, but i am totally in favor of Michael Bennet: we must focus on what can be done to prevent it and not on fighting it, because we are becoming too dependent on others, we are always taking the easy and short way, when it only takes a simple, small, and collective effort of each one of us to make this world a better place. Think about it.
Reply | Report Abuse | Link to thisEdward Aguilera
Puerto Rico
Maybe i am just a tenth grader and yes i didn't even know about this MRSA thing until i read this article, but i am totally in favor of Michael Bennet: we must focus on what can be done to prevent it and not on fighting it, because we are becoming too dependent on others, we are always taking the easy and short way, when it only takes a simple, small, and collective effort of each one of us to make this world a better place. Think about it.
Reply | Report Abuse | Link to thisEdward Aguilera
Puerto Rico
Maybe i am just a tenth grader and yes i didn't even know about this MRSA thing until i read this article, but i am totally in favor of Michael Bennet: we must focus on what can be done to prevent it and not on fighting it, because we are becoming too dependent on others, we are always taking the easy and short way, when it only takes a simple, small, and collective effort of each one of us to make this world a better place. Think about it.
Reply | Report Abuse | Link to thisEdward Aguilera
Puerto Rico
You are one very impressive 10th grader. I look forward to one day seeing your name among the leaders who achieved great success in helping others. And I will be applauding you Edward Aguilera!
Reply | Report Abuse | Link to thisAs someone who has been treating cases of MRSA and VRSA for many years, with near-complete success and without the use of antibiotics, I think it is diabolical to fund further research, when a solution already exists. If the corrupt politicians, decision makers and medical fundamentalists would focus upon peoples health before pharmaceutical profits and their own pocket-book, then perhaps those thousands of people who have died from MRSA and VRSA infections would still be alive today. It is not MRSA that kills most people, it's the organisations that are brainwashed into believing that only pharmaceutical companies can come up with the right answer. I fully agree with the comments of Michael Bennett. In the ever-changing pathogenic world of bacterium, where bacteria can form resistance faster than the pharmaceutical companies can devise new products, there is no sense in persuing this course of action. Do I believe that the product I use is effective? Most certainly. It has cut its teeth over the course of the last 5 years on even the most difficult of cases. We even succeeded where 30 days of intravenously administered Vancomycin failed, in a patient who had suffered with MRSA for nearly 4 years. Prevention? That is where they all get it wrong. The right way in prevention is to immunise the patient, as well as the surroundings. Treatment prior to admission would not only protect the patient, but build up the immune system and eradicate many other pathogenic bacterium before admission. Cleaner wards, pathogen-free patients, greater immune system function, would lead to better recovery times, no delays in operation schedules and more patients being treated. While this has made enormous sense to me, over the five years that I have run my MRSAmedical.com website, just who listens or cares? I have come to the conclusion that I can only help people on a one-to-one basis, as red-tape and corruption spoils the bigger picture. Yes, I have been there, experienced the slings and arrows and returned in disgust. Self-indulgence seems a greater priority than the lives of the masses. What a pitiful and disgusting world we live in. Thousands of people dying every year from MRSA because the pharmaceutical companies funds must be protected. MRSA killed more people in the USA last year than AIDS, along with over 1,000 pets. One of the latest responses from a patient contained information that her doctor had stated 'pets don't get MRSA.' My advice: Change your doctor!
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Technology is not going to save us from these issues. In fact, technology is partly to blame, since that is what enabled us to continue with our bad habits far longer than we otherwise would have.
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