Superbug Contagious Gene NDM-1

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inga's picture
inga
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Superbug Contagious Gene NDM-1

While preparing for a medical procedure, (here in the US, and orthopedic)  I decided to research the latest supergerm...It isn't a super germ....It's a super gene.  Now it appears that it isn't killing volumes of people....not yet, I guess.  See what you think.  I have a medical background and this one concerns me....because of HOW it works.

http://www.cnbc.com/id/38677723/Warning_to_Travelers_About_New_Drug_Resistant_Superbug

Notice this comes from my 'medical' source, cnbc. LOL

Another source....

http://news.yahoo.com/s/ap/20100913/ap_on_he_me/us_med_superbug_gene

I blew it off originally, since it came across the news media as a 'superbug' and I figured they would have a 'cure' pretty fast, or it was some hard to catch thing.  It isn't a superbug, it is a plasmid or genetic material.  It can splice itself to ANY germ, and apparently confer antibiotic resistance....and it can cause a supergerm every time a person passes it one to another, since it splices into any bacteria.  I believe so far, it is just bacteria, not any other organism, if you call a virus an organism.  Given viruses are basically gene factories....

Thought some may be interested in this, since it is  basically a contagious gene, spread from hand to mouth contact.  Likely it is all over the world by now, since who really monitors infections in 3rd world countries?  People literally drop like flies from infection in many countries.  I did think the next major germ could evolve in the Pakistan floods.....close....I guess...duh, lots of people stuck together, sewage, lack of sanitation--stir well.  It could be anywhere in a disaster....not picking on Pakistan....they just happened to have floods, and a lot of people.

 I haven't found much on this on WHO sites....well, ok, I have found nothing on WHO sites.  Goes to show, when you want info...your source on medicine, cnbc.

The 4 reported US cases did survive.  I do not know what treatment they were given.

Oh well for what it is worth, interesting bedtime reading, and as far as any cosmetic surgery....I will pass...getting old and ugly seems the better choice.

inga's picture
inga
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Re: Superbug Contagious Gene NDM-1

Oh dear, this is a bit more pessimistic.

http://www.indiatalkies.com/2010/09/japan-confirms-cases-delhi-superbug.html

 

Oh well, off to the mall!!

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jrf29
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Re: Superbug Contagious Gene NDM-1

Is it a cause for concern?  Yes...and no.

Most antibiotic resistance factors travel on plasmids, and as a matter of fact, the first antibiotic resistance factors ever discovered were plasmid-mediated.

A plasmid is basically a mini-chromasome.  The genome in bacteria consists of one gigantic loop of DNA.  The enzymes which replicate a genome (called DNA polymerases), can only get started at certain points on the chromosome where there is a so-called "origin of replication" -- a series of base pairs in a particular seqence that the DNA polymerase can recognize and bind to.  Any strand of DNA that contains its own origin of replication is called a "replicon," because it can replicate on its own.  A plasmid is a simple replicon.  Most plasmids contain other genes that facilitate their transfer between bacterial cells - this ensures their survival.  They aren't viruses, because they cannot exist outside a cell for any period of time -- they must be passed down through generations of the same cell line, or be transferred directly from one cell to the next.  They cannot pass through the air or in water like a virus can.

A plasmid can contain a single gene, or any number of genes.  In fact, you can create your own plasmids in the laboratory and insert any gene that you like into them.  Now, it is not surprizing that a plasmid containing resistance genes for multiple antibiotics eventually turned up - we always knew that continued use of antibiotics would apply this type of evolutionary pressure to bacterial populations.  Of course, there are already plasmids which contain genes coding for resistance to many individual antibiotics, or to two or three of them together. 

It is always possible for a bacterial cell to be infected with multiple individual plasmids, giving it resistance to many (or all) antibiotics.

But here, all of the genes for resistance to many antibotics are clumped on a single plasmid.  The take-home message is that resistance to antibiotics is growing worldwide.  It has been growing for a while.  The science media is taking this opportunity to demonstrate that we really need to do something in the way of developing new antibiotics.

So, if you are going into the hospital for a surgical procedure, is the existence of antibiotic resistant bacteria bad news?  You bet.  It is a real threat.  In a hospital that is currently experiencing an outbreak of resistant bacteria, you are essentially being asked to have surgery in a 1925 hospital.

But does the existence of this resistance plasmid mean that we have to worry about it sweeping the globe in a matter of years, making all bacteria everywhere immune to all of our antibiotics?

No.  For several reasons:  First of all, we have to remember that bacteria and fungi have been producing antibiotics naturally for tens of thousands of years (and longer), and the individual genes which give bacteria resistance to particular antibiotics have been around for quite a while also.  So if the genes have existed for thousands of years, why doesn't every sensible bacterial cell carry around copies of all these genes, just in case?

The answer is because these genes are "expensive."  It takes a lot of a cell's energy to repicate DNA, and plasmids are no exception.  It's like carrying a monkey on your back.  In addition to having to devote energy to replicating your plasmid, the antibiotic resistance genes on the plasmid code for the production of complicated chemicals which take even more energy for the cell to manufacture.  And this new plasmid has genes on it which code for resistance to just about every antibiotic under the sun!

What does that mean?  It probably means that this plasmid is humongous.  It's the bacterial equivalent of having a Picasso hanging in your living room -- very expensive.  Or, the bacterial equivalent to having ten monkeys on your back.

Therefore, bacteria which carry this particular plasmid will devote a very large amount of their cellular energy tending to this plasmid.  In a normal environment, they will grow more slowly and divide less efficiently than bacteria without the plasmid.  In most environments they will not be able to compete efficiently against bacteria not carrying the plasmid,

The only place where these plasmid-infected bacteria could effectively compete against non-plasmid strains is in intensive care wards, burn units, and similar medical environments where antibiotic use is very, very high.  They probably wouldn't even be able to reproduce efficiently in a normal hospital ward, since there are only a few commonly used antibiotics there, and it would be more efficient for them to simply carry resistance genes to those antibiotics alone.  That is why this new strain is associated with "medical tourism." 

NDM-1 laden bacteria will never be able effectively complete against normal bacterial populations in your home or office, because in these environments (where there are no antibiotics) the enormous monkey on their backs does them no good in competition with other bacteria.

This provides a second bit of good news: if we stop over-using the antibiotics, the bacteria with these kinds of plasmids will slowly be out-competed by more efficient wild-type strains.  If worse came to worst, we could simply stop using a certain class of antibiotics for a few years, and wait for the resistant population to die back.  This was tried in Finland with macrolide antibiotics, and it worked very well.

Finally, we have to remember that all bacteria (like every other organism) have mechanisms for recognizing which genes belong to them and which don't.  They do this by methylating certain sequences of base pairs in their DNA, like a secret code.  Any fragment of genetic material that doesn't carry the correct secret password is attacked and digested by the cell.  This makes it hard for plasmids to hop willy-nilly between species.  It can be done -- the plasmid has to survive one reproduction cycle of the infected cell, after which it will be methylated in the appropriate places by the cell's normal genetic machinery.  But most times, the plasmid will not survive natural introduction into a foreign bacterial species.  This does much to keep a plasmid confined to the species which it currently inhabits.

So: Is bacterial antibiotic resistance cause to worry if you are planning on spending time in an intensive care ward?  Sure.  It always has beena worry, and the problem is getting worse every year.  But will this plasmid sweep the world and make all bacteria resistant to all antibiotics?  No, not a chance, for the reasons above.

inga's picture
inga
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Re: Superbug Contagious Gene NDM-1

Thanks for the info, and I will be in and out for day surgery....not necessarily unrisky since it is orthopedic....not optional tho.  The fact that we are looking at some pretty nasty hospital borne infections is not news, but, this one seems more concerning. What you are saying makes lots of sense.  I am wondering if it got a foothold, or is this only news because GSK has some patent?

Anyway, this thing has hopped to generic E coli and Klebisiella...apparently it is getting into garden variety germs, not just hospital ones....that said, the people who got this, were in hospitals in India and Pakistan.  Some died of the infectious diseases, others of the original problem.

So this one is different in that is bestows such a huge resistance to antibiotics?  And you think the sheer size of the plasmid will limit it?  Medscape put out a video for their subscribers and I thought that was really odd.  Dated 9-9-2010.

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SteveW
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Re: Superbug Contagious Gene NDM-1

jrf29, that was an excellent summary.

I think the only thing I can add is that the Russians many years ago looked into using bacteriophages, viruses that will attack specific bacteria, as a method of killing germs without antibiotics. Wikipedia has a good summary. http://en.wikipedia.org/wiki/Phage_therapy

I suspect that this treatment method has had little research due to the inability to  patent naturally occurring phage organisms and generate obscene profits.

 

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Tall
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Re: Superbug Contagious Gene NDM-1

"Therefore, bacteria which carry this particular plasmid will devote a very large amount of their cellular energy tending to this plasmid.  In a normal environment, they will grow more slowly and divide less efficiently than bacteria without the plasmid.  In most environments they will not be able to compete efficiently against bacteria not carrying the plasmid,

The only place where these plasmid-infected bacteria could effectively compete against non-plasmid strains is in intensive care wards, burn units, and similar medical environments where antibiotic use is very, very high.  They probably wouldn't even be able to reproduce efficiently in a normal hospital ward, since there are only a few commonly used antibiotics there, and it would be more efficient for them to simply carry resistance genes to those antibiotics alone.  That is why this new strain is associated with "medical tourism.""

This is certainly a reassuring statement, but is not supported by the scientific evidence.  Rates of community acquired (meaning the person acquired the infection outside of a health care setting) antimicrobial resistant infections such as MRSA are increasing steadily in most US populations.

Additionally, we are unaware of all the potential evolutionary advantages to to the organism associated with these genes. Anti-microbial resistance genes are freely shared among genera even without continued antimicrobial exposure and are known to confer additional benefits to the organism such as resistance to heavy metal toxicity. 

Here is a recent paper that documents increased antimicrobial resistance among environmental organisms over time, far outside a hospital setting: http://zembla.vara.nl/fileadmin/uploads/VARA/be_users/documents/tv/pip/zembla/2010/knappDolfingEhlertGraham10.pdf

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jrf29
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Re: Superbug Contagious Gene NDM-1

Hi Tall,

Thank you for the article.  That was a very interesting study, and I'm glad to have read it.  As you remind us, the use of antibiotics in medicine isn't the half of it.  Tons of liquid antibiotics are sprayed over crops, not to mention the antibiotics added to poultry feed in order to increase meat yield.

The journal article which you posted is significant for our purposes because all of the soils tested were agricultural soils.  The overuse of antibiotics in agriculture is widely recognized, and the bacterial populations of these soils have probably been regularly (if not continuously) exposed to antibiotics for decades.  In essence, these fields are the equivalent of the hospital intensive care ward: a breeding ground for resistant strains.

The study authors confirm this:

"Given that environment protection seems to be improving, the question is why might ARG levels be still increasing now?  In our case, the answer may lie in specific practices in The Netherlands, although such local activities are not uncommon around the world. For example, despite greater emphasis on conservative antibiotic use in agriculture, a surprising increase in use has occurred in The Netherlands since 1997 (see Figure S3; (37)). The actual reason for this increase under the more stringent European rules is under debate; however, this increase mimics increases in ARG levels at sites D and E, especially associated with tetracyclines..."

Essentially, this confirms what we would expect: that continued (and increasing) application of antibiotics to an environment will lead to increased resistant bacterial populations.  It would be fascinating to see the results of a study that looked at ABANDONED agricultural sites five or ten years later, to determine whether the resistant bactrial population remained elevated.  But, alas, this study did not do that.

Even though I haven't seen a study, I would speculate that the levels of antibiotic resistant bacteria in normal human environments are also increasing.  After all, hospital patients have to come from somewhere (the community) and after they leave the hospital they go back to the community.  There are some parts of the world (like Finland prior to the macrolide elimination experiment) where some degree of resistance to common antibiotics (especially penicillin and tetracyclines) is almost universal, and starting dosages are two and three times what they were years ago, if the antibiotics are still effective at all.

Understand that I'm not trying to down-play the importance of antibiotic resistance as a public health threat.  I agree that the rates of antibiotic resistance are climbing and accordingly, the number of resistant strains in the environment is also increasing as a result of our continued overuse of the drugs.

But the news articles seemed to imply that this new plasmid was like a virus that could sweep through bacterial populations, rapidly making them immune to all of our antibiotics.  That's the misperception I was aiming at.

I would emphasize the following points from what I said earlier:

(1)  Each antibiotic or class of antibiotics generally has its own resistance gene associated with it.  I.e., no matter how widespread the gene for gentamycin resistance, this does not give any resistance to amikacin.

(2)  The expensive second and third-line antibiotics that are used in hospitals are not used in agriculture.  These antibiotics are expensive (too expensive for people on the street in 3rd world countries to buy and use willy-nilly) and their use is largely confined to professional medicine.

(3) Resistant bacteria for the last-ditch antibiotics do exist, and they are spreading.  BUT, and this is the big "but," resistance to these types of antibiotics will always be concentrated around medical facilities and other places where antibiotics are used the most, and bacteria which carry these huge enormous plasmids will always have a harder time surviving outside the medical environments which bred them (just as the bacteria in the study you cited would have a tough time thriving outside of the antibiotic-soaked fields which spawned them).  In other words: this plasmid won't sweep the world and make all bacteria resistant.

Finally, it is true that we are unaware of the additional competitive advantages which antibiotic resistance genes might afford to their host cells.  However, the fact is that the bulk of resistance genes are not new -- they have been around for eons.  If these genes provided such a competitive advantage, then I (at least) would expect to see them much more widely distributed in natural bacterial populations.

Thanks again for the article and discussion, Tall. 

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Tall
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Re: Superbug Contagious Gene NDM-1

Hi jrf29,

We both agree that antimicrobial resistance increases in settings where antimicrobials are used.  That is well established.  My point in joining this discussion, is that antimicrobial resistance appears to be increasing in bacteria far outside of these settings as well.

 I remember my Aha! moment about 10 years ago when I read a paper that discussed the transmission of antimicrobial resistance among bacteria (many of them human pathogens) in the Enterobacteriaceae family (E. coli, Enteroboactor spp., Salmonella spp., Klebsiella spp., etc) even in the absence of continued antimicrobial pressure.  At that time, I made the comment to a colleague that it appears that we have opened Pandora’s Box for antimicrobial resistance.  I am currently unable to find that paper in my hard archives, if I do I will post the citation as I was very impressed by the work and would like to share it with you.

However, there is more recent work that supports that same finding of significant antimicrobial resistance without apparent antimicrobial pressure, suggesting that antimicrobial resistance genes confer survival benefits to the organism of which we may be unaware.

 

See: Foodborne Pathog Dis. 2010 Aug 12. [Epub ahead of print]

Characterization and Transferability of Class 1 Integrons in Commensal Bacteria Isolated from Farm and Nonfarm Environments.

Yang H, Byelashov OA, Geornaras I, et al

 Abstract This study assessed the distribution of class 1 integrons in commensal bacteria isolated from agricultural and nonfarm environments, and the transferability of class 1 integrons to pathogenic bacteria. A total of 26 class 1 integron-positive isolates were detected in fecal samples from cattle operations and a city park, water samples from a beef ranch and city lakes, and soil, feed (unused), manure, and compost samples from a dairy farm. Antimicrobial susceptibility testing of class 1 integron-positive Enterobacteriaceae isolates from city locations displayed multi-resistance to 12-13 out of the 22 antibiotics tested, whereas class 1 integron-positive Enterobacteriaceae isolates from cattle operations only displayed tetracycline resistance. Most class 1 integrons had one gene cassette belonging to the aadA family that confers resistance to streptomycin and spectinomycin. One isolate from a dog fecal sample collected from a city dog park transferred its class 1 integron to a strain of Escherichia coli O157:H7 at a frequency of 10(-7) transconjugants/donor by in vitro filter mating experiments under the stated laboratory conditions. Due to the numerous factors that may affect the transferability testing, further investigation using different methodologies may be helpful to reveal the transferability of the integrons from other isolates. The presence of class 1 integrons among diverse commensal bacteria from agricultural and nonfarm environments strengthens the possible role of environmental commensals in serving as reservoirs of antibiotic resistance genes.

BTW- your point about the agricultural fields being under antimicrobial pressure ("antibiotic soaked fields") is not necessarily true.  My understanding is that animal agriculture and pomiculture (pome fruit orchards) are the only agricultural environments that use antimicrobials during production.  Do you have other information?

I guess my point in all this is that we should not be complacent on this issue: we all have some risk of infection with antimicrobial resistant organisms, even outside of a health care or animal production setting.  It is good practice to take care of even small breaks in the skin, to practice proper food handling when preparing raw meat, eggs and raw milk, and to wash our hands before we eat. 

As far as NDM-1, it remains to be seen how it will be expressed among pathogens and environmental bacteria. I am sure that many will be watching.

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Tall
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More spread of environmental antimicrobial resistance

BACTERIA that can resist nearly all antibiotics have been found in Antarctic seawater.  (Human sewage appears to play a factor in introduction of these organisms.)

Recent work shows the bacteria may hang on to the genes for CTX-M even when no longer exposed to antibiotics and that superbugs can survive in the wild, with animals acting as a reservoir. Penguins near the Chilean stations have been checked and are free of ESBL, though Olsen is now looking at the area's gulls as he has found ESBL-producing bugs in gulls in France.

http://www.newscientist.com/article/mg21328494.200-superbugs-spied-off-the-antarctic-coast.html

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