E. coli O104:H4 in Europe--is it new?

Mike has has a great new post up looking at some molecular analyses of the current European outbreak strain. For anyone who hasn't been paying close attention to what's happening across the pond, there's an ongoing outbreak of enterohemorrhagic E. coli (EHEC)--the type of E. coli that includes O157:H7, which has been associated with outbreaks of disease associated with food. The most infamous outbreak was the 1993 Jack-in-the-Box disaster, associated with undercooked hamburgers contaminated with the organism, but there have also been outbreaks associated with contaminated vegetables (such as the 2006 outbreak due to spinach). Infections with this bug can cause serious illness, including bloody diarrhea (due to production of a protein called the Shiga toxin) and eventually can shut down the kidneys. Permanent damage can result, and even death.

In most outbreaks, children have been the most affected group, and the outbreaks tend to be fairly small (as outbreaks go--~200 people were confirmed to be infected due to spinach in 2006, though many more mild or asymptomatic cases likely went undetected). That's reason number 1 this European outbreak is a bit odd. Adults are the largest group affected, and of those, most have been women. It's also a huge outbreak--at least 1600 affected and 16 deaths to date. Almost a third of those--roughly 500--have been diagnosed with hemolytic uremic syndrome (HUS), one of the most serious complications of the infection. That's a huge number, and cases don't seem to be slowing down, as we usually see with EHEC outbreaks.

News out yesterday also includes notice that one of the outbreak strains has been sequenced:

Meanwhile, a Chinese genomics laboratory, BGI (formerly the Beijing Genomics Institute), announced today that it has sequenced the outbreak strain and completed "a preliminary analysis that shows the current infection is an entirely new super-toxic E coli strain." The analysis was done by BGI-Shenzen in collaboration with the University Medical Centre Hamburg-Eppendorf, the BGI statement said.

The analysis confirmed that the pathogen is an E coli O104 but said it is a new serotype, "not previously involved in any E coli outbreaks," according to BGI. The strain is 93% similar to a strain found in the Central African Republic, but it has acquired sequences that seem similar to those involved in causing "hemorrhagic colitis" and HUS, the statement said.

The statement also said the E coli strain carries genes that confer resistance to several classes of antibiotics. Earlier reports from Europe had said the strain was resistant to multiple drugs.

A WHO official agreed that the outbreak strain is new, according to the AP report. "This is a unique strain that has never been isolated from patients before," said Hilda Kruse, a WHO food safety expert.

Earlier this week, the CDC called the outbreak strain very rare but not brand new. In today's AP story, Dr. Robert Tauxe, a CDC foodborne disease expert, said the strain was seen in a case in Korea in the 1990s. He said the genetic fingerprints of the current strain and the Korea one may vary slightly, but not enough to call the European strain new, according to the AP.

I believe that this is the Korean paper they're referring to, describing a case of O104:H4 infection, but it's not from the 1990s, at least that I can tell (published in 2006, though it may be an old case). Mike is skeptical that this is a new strain as well. The wording of the article doesn't make sense either; O104:H4 *is* the serotype, so that obviously isn't novel, though some elements of the bacterium could be. Reports are saying that it produces more toxin than ordinary EHEC strains, and that it's resistant to multiple antibiotics. For these infections, the former is important; the latter, not so much, as treating EHEC infections with antibiotics actually makes the infection worse. (However, E. coli can also cause other types of infections, including meningitis and septicemia, for which antibiotics would be appropriate--so it's not completely OK that it's multi-resistant; it just doesn't matter as much for the diarrhea/HUS combination).

So what's going on? Still hard to tell. We don't yet know the vehicle for bacterial transmission. Salad ingredients--lettuce, tomatoes, and cucumbers have been implicated in case-control studies but no one has yet found this strain on vegetables. We don't really know if the virulence in this strain is higher than other EHEC strains, or if the higher apparent levels of HUS are due to better reporting/surveillance in Europe. (I think this unlikely--it's a pretty large difference--but still, it needs to be examined). Basically, we're closing in on a month into this outbreak and we still know very little, and it doesn't seem to be slowing down at a rapid pace. And, we probably haven't even identified all the cases to date--there have now been three diagnosed in the U.S. following travel to Germany, and likely more sporadic cases in other areas that haven't been linked back to this outbreak yet. Stay tuned; this one's going to be in the news for awhile as we get it all figured out.

Edited to add: see also other posts on this, especially the sequencing/novelty issues, here at phylogeo, here at bacpathgenomics, here at pathogenomics, or here at genomic.org.uk.

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forgive my naivety but what is the difference between E.coli ST678 and the P678-54 E.Coli often used in experimental biotechnolgy

Hope you can help

By Dave Roberts (not verified) on 03 Jun 2011 #permalink

I'm not familiar with that particular strain, but the ST refers to (as explained in Mike's post and some links within) an algorithm of sequences of housekeeping genes, which together provide the "sequence type" of the isolate (in this case, 678). The other one just appears to be a strain name, originating in the 1960s, well before multi-locus sequence typing (MLST)--so the 678 in both of them would appear to just be a coincidence.

is this bacteria carried on the outside of the vegitables,
or is it possible to have been absorbed or transported into / through
the vascular system of the plants in the irragation water ?

I thought there was a study by researchers in Aberdeen showing some E coli can invade lettuce leaves as well as being present on the surface. I'm on my phone atm so can't track it down but will try to find it when I get home.

There have been reports of E. coli inside vegetable tissues ("internalized"), check out Keith Warriner's papers. Also, migration from roots to shoots has been shown with some strains of E. coli. It wouldn't surprise me that they can be inside. Gadi Frankel showed active stomatal tropism in EHEC. On a "distantly related" matter, Salmonella can internalize actively in the apoplast of leaves, there are very nice microscopy studies on this. Sorry I don't have links to the papers right now but can post later if interested.

Do you happen to know whether this outbreak is unusual in causing neurological disability? One worry that's prominent in German media is the fear that in addition to the death toll, many of the patients might survive but not recover cognitively.

There was, and is, a lot of confusion over the use of antibiotics and eculizumab in treatment, so it's not just a question of translation: German media are confused, about everything from whether antibiotics are being used to whether to avoid cucumbersâwhich remain on sale at discounted prices.

"Looks like it's mostly external, but I'm not familiar enough with the literature to know if there are other studies disputing this one."

Posted by: Tara C. Smith | June 4, 2011 1:23 AM

Thanks, good link too.

zoonotica or phylogeo, if you could post some papers, that would be great. I have limited access right now and found one Warriner paper (PMID:16355819) but that doesn't seem to support E. coli in the leaves. I can only read the abstract right now, though.

I am a researcher with EU parliament, and am looking into the EHEC cases in Germany, I would be very interested in the impressions of those in epidemiology on this particular strain.. I welcome any of your opinions on this, it seems an awfully large number of people being infected in a very short time span.. especially the numbers of those with HUS, and the fact that they are adult/ and mainly women..


Is this strain of E.coli sorbitol fermenting(like EC O O57 h7) or non sorbitol fermenting?

I don't have access to Warriner's papers either, sorry. I have them in print somewhere though. I was maybe a bit too fast in my previous comment, as it seems some people object to E. coli internalization relevance in natural conditions based on the fact that it's been observed only with very high inocula. Technical problems, then. I can't really say more about that sorry. However, I came across a very nice review on human pathogens vs. plants and studies supporting the fact that some could live endophytically (inside plant tissues) available here:

The other studies I mentioned:
- http://aem.asm.org/cgi/content/full/74/9/2908
- http://scholar.google.co.uk/scholar?cluster=2293104656833012916&hl=en&a…
- http://scholar.google.co.uk/scholar?cluster=3764074265009415895&hl=en&a…

Hope this helps.

Ben bir doktora kimyager olarak tanıÅtıÄında 25 yıl önce ortak bir yanıt oldu: ". Bir bilim adamı gibi görünmüyor" Åimdi ortaya ortak bir tepki "Neden tek mi?",'s Insanlar bazı aptal Åeyler söylüyorlar. Tam olarak deÄil haber.


This is what I've found so far:

Transmission of Escherichia coli O157:H7 from Contaminated Manure and Irrigation Water to Lettuce Plant Tissue and Its Subsequent Internalization by EB Solomon et al (doi:10.1128/AEM.68.1.397-400.2002) shows E coli can be taken up by the plant via its root system.

[I haven't been able to read this one but somebody might have access: Penetration of Escherichia coli O157:H7 into Lettuce Tissues as Affected by Inoculum Size and Temperature and the Effect of Chlorine Treatment on Cell Viability by Takeuchi et al. J of Food Protection 63(4) 434-440

I also can only access the abstract of: Attachment of Escherichia coli O157:H7 to Lettuce Leaf Surface and Bacterial Viability in Response to Chlorine Treatment as Demonstrated by Using Confocal Scanning Laser Microscopy by Seo KH et al J of Food Protection 62(1) 3-9

Both of the above abstracts and papers that reference them suggest that E coli can invade at cut leaf edges sufficiently to avoid killing by chlorine treatment.]

I'm surprised only two articles have appeared on Scienceblogs so far. In European newspaper, it's all over the front pages, and it's clearly the most reported-on news of the last week. Sadly, most articles aren't half as informed as yours.

I did try to post a comment yesterday with some papers but I got a message saying it got held in moderation.
Let me know if I need to post it again

Apologies--indeed they got caught in moderation, and I've not been on much in the past 24 h. to get them out. Published now, thanks!

@10. Close the restaurant in Lubeck, the only reference for origin. Test it at least for a month. Customers have been eating fresh food on that sort of cemetery / hospital. Look for documents to open the restaurant and reforms made. Look Black Pestis in Germany, Yersinia Pestis. Check the restrooms, pipes, ground level of the building (no rats and no bugs?). Medical test of all workers. 40 days ban (old style means) to the German products in each country, plus medical tests of any traveler from Germany?

As a former microbiologist, I must admit that my first lean in the question of why this bug appears to be affecting adults and women more is toward virulence characteristics; however, dietary habits, i.e. the tendency for children to avoid certain foods due to texture issues, e.g. tomatoes (hard bite then soft and mushy) may be the key here. Likewise, many women seek to lose/maintain weight by eating salads. Food choice, rather than virulence characteristics may explain the unusual distribution. Wonder whether they're checking the cabbage?

By Dr. James England (not verified) on 07 Jun 2011 #permalink