By Vanesa Segovia
If you have seen movies like CONTAGION, you will be surprised to know that they are not entirely into fiction. From May to September, 2011, over 4000 cases and around 50 deaths were reported in 16 in countries of North America and Europe [1]. All of them had typical symptoms of gastroenteritis, stomach pain, nausea and bloody diarrhea, but additionally they had the lethal syndrome of HUS (Haemolytic Uraemic Syndrome), which destroys red blood cells and causes kidney failure. The outbreak originated in Germany and the responsible was an E. coli variant (strain) named as O104:H4, which very quickly was identified, the genome was sequenced and the pathogen characterized. In record time, and according with the genome sequence information, the reason why this strain was so virulent was unveiled [2], which allowed an immediate response from the doctors, enabling the right medical treatment and proper strategies of disease control to block the dispersion of this little enemy.
The unprecedented global crowd-sourcing effort did make possible to stop the dispersion. Scientist around the world collaborated to facilitate the characterization of this bacteria, the specialists provided the bases to generate a platform that allowed data analysis, comparisons and conclusions in a short period of time [3]. The genome analysis centre-TGAC, in Norwich, England, was one of the research centers involved in performing this important task. BIOGENIC had the chance to talk to Dr. Lisa Crossman (Microbial Genome Project leader at TGAC), who was directly involved on the characterization of this bug, and who was very generous to answer our questions about this outbreak; she also shared with us part of her experience as a young scientist.
1. Dr. Crossman, where are you from?
I was born in Malaysia and I grew up in Europe. I live in Norwich in the East of England since my PhD.
2. What events shaped your career choice?
Family (my father is a biologist), my own interests and my children.
3. How would you describe working in scientific research?
Everything from the routine to the most exciting thing!
4. We are curious, you are a young project leader in TGAC’s. Which is the trick to achieve your goals in such a short period of time?
Unfortunately I do not think there is a trick, just work hard and play hard.
5. You are involved in the analysis of the E. coli O104:H4, an outbreak ranked as the second largest and most deadly in history [4], is this a new strain?
This strain is not new, however, it was originally described as new by doctors after an attempt at serotyping the strain with a bank of common serotypes, which failed due to the O104:H4 serotype being more rarely associated with this type of outbreak. Hence the original description as new until the correct serotype was identified. (Serotype refers to distinct variations within a subspecies)
6. If not, where does it come from, which are the closest ancestors?
This is still a cause for debate, however, the outbreak is believed to have been associated with beansprout seeds (served in salads). Even though we have a lot of E. coli strains sequenced, we do not have ALL E. colis sequenced so we can only compare it to the nearest sequenced neighbors. Crowd-sourcing identified the E. coli 55989 as the closest sequenced neighbor, identified in approximately 1999 involved in serious diarrhea disease in Central Africa. The chromosomes of these strains are closely related, however, the German outbreak E. coli strain has lost a small piece of DNA that can be easily traded with other bacteria known as a plasmid from the 55989, and gained three other potentially vital plasmids.
7. Why is it deadly?
It is likely to be a combination of factors. One important factor is the presence of a bacterial virus, or Phage which specifies a toxin known as Shiga toxin likely involved in the most severe symptoms of the food poisoning. Another is the presence of structures on the outside of the cell that we know are involved in aggregation, or sticking to each other and potentially to surfaces. There are also numerous genes that code for ‘nasty’ products such as enzymes that could act on our cells. Additionally, there is a high level of antibiotic resistance, however, antibiotics are not usually used to treat these bugs carrying Shiga toxin as antibiotics may in fact allow faster release of the toxin from the bacterial cells.
8. Physiology studies take some time to fully understand a pathogen. But this time we got information really quickly, due to a rapid analysis that was performed around the world. What was the strategy to generate and to perform analyses that deal with such a large amount of information?
A large group of scientists got together as a Crowd-Sourcing project where we shared a lot of information over the internet. People used many different tools to carry out analysis in their particular areas of expertise. It was very fast and fun to share, people were working very hard!
9. Is it possible to predict if a harmless E. coli strain will turn into a lethal one?
I would say not (at the moment anyway) it could be a case of trading genes with another bacterium and being in the wrong place at the wrong time. However, this strain had a lot of ‘nasty’ factors sprinkled throughout the sequence so it would seem to be at a higher risk of becoming lethal than another strain with less of these factors.
10. What were your most interesting findings?
One of the two plasmids picked up recently (not present in a very closely related 2001 outbreak strain of O104:H4) is the most different part of the genome sequence to other E. coli sequences. It encodes an aggregative factor and has many mobile elements, or ‘jumping genes’. Large concentrations of ‘jumping genes’ are found near the antibiotic resistance genes as well, but are found in much lower amounts throughout the rest of the sequence. It is traditionally known that these genes are involved in genetic transfer from other organisms by ‘jumping’ them out of their current position into the new one. Many of the ‘jumping genes’ found on the plasmid are not the same sort found on the chromosome or genetic backbone of the E.coli. Maybe this suggests that these pieces of DNA have come from different origins.
11. What is the next step to fully understand O104:H4?
Everyone always wants more data, so more sequences would be nice, to put this organism in context. We still need to search for a reason why this organism has been able to affect otherwise healthy adults instead of the more usual demographic which is infants and elderly people.
12. Analyses were done in the sequence rather than the O104:H4 strain, this allows to know about pathogen features, like resistance to antibiotics. Which is the role of whole genome sequencing strategies in epidemiology? (Epidemiology refers to the study of health-events, characteristics and determinant patterns in a population).
Whole genome sequencing is just knocking at the door of epidemiological studies. The reason why this is happening now is due to recent increases in speed of both sequencing and analysis and decreases in price. Sequence information could inform on tracing a route of an organism from country to country.
There is still no substitute for questioning of the patients to find a common factor in a group, for example going to a particular shop or restaurant. Genome sequencing and analysis is very powerful but it does not tell us at which shop or restaurant a contaminated product was found.
One thing found early on in the outbreak by BGI, China was a specific genetic sequence for use to speedily identify that a person has contracted this particular strain and can therefore be treated appropriately. Knowledge of antibiotic resistances carried could help in cases where antibiotics were used.
13. Can we say that bioinformaticians are able to save lives?
I think so, although it is difficult to quantify as the bioinformaticians are involved quite early on. For example, in identifying a possible vaccine target which then may go on through clinical trials etc. to become a useful vaccine.
14. How do you think that science can build up a better society?
Perhaps through teaching and outreach activities to help the public better understand issues like microbiology and health and that bacteria can both be good and bad.
15. What would be your advice for the new generation of scientists?
Science is cool, come and join in!
16. Any last ideas that you would like to add?
New methods of sequencing and analysis are moving so rapidly that new technologies and tools are likely to be in use by next year. New data for outbreak E.coli may be available or new tools to look at the existing data in a new way could change how we look at this bug! It is a really fast moving field.
References
[1] Buchholz, U., Bernard, H., Werber, D., Böhmer, M., Remschmidt, C., Wilking, H., Deleré, Y., an der Heiden, M., Adlhoch, C., Dreesman, J., Ehlers, J., Ethelberg, S., Faber, M., Frank, C., Fricke, G., Greiner, M., Höhle, M., Ivarsson, S., Jark, U., Kirchner, M., Koch, J., Krause, G., Luber, P., Rosner, B., Stark, K., and Kühne, M. 2010. German Outbreak of Escherichia coli O104:H4 Associated with Sprouts. New England Journal of Medicine 365: 1763–70
[2] Crowd-Sourcing the E. coli O104:H4 Outbreak. September 4, 2011. In Science Daily, [http://www.sciencedaily.com/releases/2011/09/110904215952.htm]
[3] E. coli O104:H4 Genome Analysis Crowdsourcing. [https://github.com/ehec-outbreak-crowdsourced/BGI-data-analysis/wiki].
[4] Marler, B. German based E. coli O104:H4 Outbreak is now second largest and most deadly in history. June 6, 2011. In Food Poison Journal, [http://www.foodpoisonjournal.com/foodborne-illness-outbreaks/german-based-e-coli-o104h4-is-now-second-largest-and-most-deadly-in-history/]
For more information please check
E. coli outbreak strain in genome race [http://www.nature.com/news/2011/110721/full/news.2011.430.html]
Microbe outbreak panics Europe. [http://www.nature.com/news/2011/110607/full/474137a.htm]
DNA Sequence Yields Clues to Germany's 'Super Toxic' E. coli Outbreak
[http://news.sciencemag.org/scienceinsider/2011/06/sequence-yields-clues-to-germany.html] Prospective Genomic Characterization of the German Enterohemorrhagic Escherichia coli O104:H4 Outbreak by Rapid Next Generation Sequencing Technology [http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022751]
Category:
deadly bacteria,
German outbreak,
sequensing
| 5 Comments
solo quiero decir que es una informacion muy valiosa.