Scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip:
Image: National Institutes of Health (part of the United States Department of Health and Human Services)/Public domain.
Natural GMOs can be really really bad and fundamentally unsafe, because Nature is not scrutinised by any human regulatory agency, and many natural GMOs get their genes from all over the place. The first investigated example of this over-the-top natural-sexual promiscuity discovered by scientists is natural gene movement to and from the gut bacterium Escherichia coli.
Joshua Lederberg’s 1946 discovery of such genetic behaviour by E. coli was heralded by Salvador Luria as likely to be “among the most fundamental advances in the whole history of bacteriological science”. Over the years we have come to realise that this natural mating behaviour is a natural process for indiscriminant injection of genes into new locations in other organisms.
It is a perfect example of the rule that natural biology comes with no guarantee of safety, and a perfect illustration that gene movement between species is completely natural. Nature simply does not come with a certificate to guarantee “gene contamination will not occur”.
E. coli comes in some varieties of germ that cause disease in humans, and many other varieties that do no harm at all to humans. The disease causing strains of E. coli can evolve naturally from safe ones by processes of gene-swapping. One form of gene swapping that they us is called conjugation (mating), and some E.coli can conjugate with almost anything. That’s what they do naturally. The biological details of conjugation are well explained by a new Guardian newspaper blog posting:
Food poisoning reminds us that bacteria do have sex | GrrlScientist | Science | guardian.co.uk
Through the wonders of bacterial conjugation, formerly friendly gut bacteria have been transformed into merciless killers lurking in your salad bowl.
Those of you who live in Germany, as I do, are probably concerned about the recent and ongoing E coli outbreak that has killed 10 people (so far) and sickened more than 1000. The news coverage provides updates on the whos, whats, wheres and whys of this outbreak, but discussions of how such events occur are lacking or incomplete, so I thought I’d fill you in.
Contrary to what you might think after seeing most news reports, not all E coli (shortened from their scientific name, Escherichia coli) are toxic: in fact, most strains are beneficial to their hosts. E coli are normal gut flora whose preferred habitat is the large intestine. They are protective because shortly after a baby is born, E coli become established in the gut, crowding out disease-causing pathogenic bacteria by filling up all available space with their sheer numbers. E coli are also beneficial; producing vitamin K2, which has a variety of functions in the body.
(More at link to GrrlScientist)
It’s fairly obvious why a bacterium would adopt a gene from a different bacterium.
What’s not obvious is why a bacterium would take the time and trouble to donate genes to others. There are metabolic etc. costs, but what are the benefits?
Imo it makes more sense to take a gene’s (for a given value of gene… I guess a plasmid’s view may be better)eye view rather than organismal – it may cost the organism to engage in gene transfer for no obvious benefit, however the gene itself benefits by spreading itself about – this has a twofold effect, primarily it can be seen as purely reproductive on behalf of the gene/plasmid of interest, secondarily it can be seen as moving into varied genetic environments rather than having all of your eggs in one basket.
Plasmids can be viewed, in this respect, as partially viral in nature – as they pass longditudanally down generations as well as horizontally they are however more likely to be beneficial than not (once you pass down the germ line it becomes beneficial to not kill the cell that reproduces you)
Hmmm… The pathogenic version of E. coli is fairly recent — it borrowed a plasmid from Shigella, and expresses shigatoxin. One thing bacteria are noted for is excreting antibiotics, to help them in the ‘turf war’ against other bacteria competing for the same enviro niche. We’d have to consider whether excreting shigatoxin helps the microbe somehow. Killing your host is not terribly beneficial, or at least, not killing the host too quickly. The host needs to stay alive for a period after infection, so that other hosts can be infected. This is one of the lessons of HIV/AIDS. Early versions resulted in quick mortality. The later, more successful versions, killed more slowly, and were therefore more widely spread.
If I were looking at this ecologically I would ask if the new strain of e. coli is filling any new niches created by changes in environmental conditions. It is persisting somewhere, somehow, in the guts of livestock and not killing them. But when it gets out it is deadly to humans. Is there something new going on in the guts of livestock that roughly corresponds historically to the arrival of this form of e. coli?
suggests that in cattle the shigella toxin may be beneficial in supressing a virus – whether or not this would lead to selection or persistence within cattle kept in an ag setting isn’t immediately obvious to me – perhaps cattle who experience less viral infections are treated less frequently (erroneously) with antibiotics which would then lead to selection for the shigella toxin expressing E.coli within the herd? (daily dose of speculation right there)
Fascinating article on the virus!
Regarding your speculation on antibiotic treatments it may be interesting to look at practices for acute infections, but then there’s this other practice that is interesting…
Nearly all livestock in confinement are given continuous low doses of antibiotics. Would be interesting to look at the historical uptake of this practice and compare to the nasty e.coli rise. Is there any correlation?
I wonder if one would be expected (does the plasmid containing the shig toxin also carry an antibiotic resistance gene?) – my hypothesis would actually implicate the use of antibiotics only as a response to disease – if your animals don’t seem sick and you don’t dose them then there is a selective advantage to the shig toxin – if you’re being dosed at levels which kill E.coli regardless then the Shig toxin would make no difference (given the prevalence of E.coli in cattle you’d have to assume they’re unaffected by the general low level antibiotic treatment) – I guess it’d be a good arguement against just tossing antibiotics at your cows without knowing what ails them – if it isn’t treatable by antibiotics then you potentially select for bacteria which keep cows healthy enough to not need treatment (which would actually be a great thing if only the responsible bacteria wasn’t pathogenic to humans)
Fairly recent in Evolution is something like 20,000 years at least, which is the emergence time estimate for E. coli O157 H7.
Inducing huge volumes of watery faeces is a wonderful way to spread in the environment. E. coli can survive quite well in the watery environment before finding another gut to colonise.
Pubmed shows a recent estimate of 400 years for divergence of two serologically distinct pathogenic strains. We can follow evolution almost in real time with bacteria.
PLoS One. 2010 Jan 14;5(1):e8700.
Derivation of Escherichia coli O157:H7 from its O55:H7 precursor.
Zhou Z, Li X, Liu B, Beutin L, Xu J, Ren Y, Feng L, Lan R, Reeves PR, Wang L.
Tianjin Economic-Technological Development Area School of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
There are 29 E. coli genome sequences available, mostly related to studies of species diversity or mode of pathogenicity, including two genomes of the well-known O157:H7 clone. However, there have been no genome studies of closely related clones aimed at exposing the details of evolutionary change. Here we sequenced the genome of an O55:H7 strain, closely related to the major pathogenic O157:H7 clone, with published genome sequences, and undertook comparative genomic and proteomic analysis. We were able to allocate most differences between the genomes to individual mutations, recombination events, or lateral gene transfer events, in specific lineages. Major differences include a type II secretion system present only in the O55:H7 chromosome, fewer type III secretion system effectors in O55:H7, and 19 phage genomes or phagelike elements in O55:H7 compared to 23 in O157:H7, with only three common to both. Many other changes were found in both O55:H7 and O157:H7 lineages, but in general there has been more change in the O157:H7 lineages. For example, we found 50% more synonymous mutational substitutions in O157:H7 compared to O55:H7. The two strains also diverged at the proteomic level. Mutational synonymous SNPs were used to estimate a divergence time of 400 years using a new clock rate, in contrast to 14,000 to 70,000 years using the traditional clock rates. The same approaches were applied to three closely related extraintestinal pathogenic E. coli genomes, and similar levels of mutation and recombination were found. This study revealed for the first time the full range of events involved in the evolution of the O157:H7 clone from its O55:H7 ancestor, and suggested that O157:H7 arose quite recently. Our findings also suggest that E. coli has a much lower frequency of recombination relative to mutation than was observed in a comparable study of a Vibrio cholerae lineage.
The Shiga toxin genes are generally carried on BACTERIAL viruses which lurk silently in the host genome for numerous generations. In E. coli O157 there are 2 different shiga toxin gene carrying viruses (called prophages).
There in not 1 only lineage of pathogenic E. coli but several, which have evolved independently. Pathogenic E. coli is a PLURAL expression, and there are many pathological types.
Interestingly, one of the world leaders on studying bacterial pathogen evolution, Mark Achtman is in Berlin. The Germans really need him now.
All the vast recent progress that has been made on understanding bacterial evolution and E. coli evolution comes from genetic engineering techniques and investigations usings GMOs.
Natural GMO? Sure, but I think it’s important to note that rates of horizontal gene transfer between bacteria are far higher than for eukaryotes, lest someone get the wrong idea. I discuss gene transfer in a post ironically named: GMOs could render important antibiotics worthless
Yes indeed Anastasia. Also the rapid rates of horizontal gene movement in bacteria makes the possibility (undetectable in practice) of gene antibiotic resistance gene movement from plants to bacteria IRRELEVANT from a safety point of view. Also the soil is a vast reservoir of mobile bacterial antibiotic resistance genes. We cannot keep soil from getting in our food however much we try.
Thanks for the clarifications (particularly on it actually being virally transmitted rather than via plasmids, that’s rather cool) – given the comparatively long time that the pathogenic strains have been around one could quite easily argue that their presence (assuming they aren’t pathogenic in cattle, which they don’t appear to be from a very quick skim) in cattle could well be down to the capacity to protect from viral infection – infact it would suggest (to me) that domestication of cattle would be a rather good culprit for a source of selection pressure for a bacterium which induced viral resistance in its host – what with viral diseases being more easily spread in confined dense populations and whatnot (I guess that’s today’s evolutionary just-so story, made all the more palatable by not being evolutionary-psychology no doubt!)
The connection between low-level administration of antibiotics to cattle, and the emergence of antibiotic-resistant bacteria in humans, has long been surmised but never proven. This is a battle that spans at least one decade.
I am under the impression — David may correct me — that low-level doses of antibiotics are fed to cattle for the purpose of promoting beneficial bacteria. Those which aid conversion of feed into beef are preferred, others are suppressed.
Didn’t Nina Fedorov discuss the virulence factor of Vibrio being carried by a Phage too?
Yes that’s true. Here is the latest on it:
Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2516-21. Epub 2011 Jan 24.
VGJphi integration and excision mechanisms contribute to the genetic diversity of Vibrio cholerae epidemic strains.
Das B, Bischerour J, Barre FX.
Centre National de la Recherche Scientifique, Centre de Génétique Moléculaire, 91198 Gif-sur-Yvette, France.
Most strains of Vibrio cholerae are not pathogenic or cause only local outbreaks of gastroenteritis. Acquisition of the capacity to produce the cholera toxin results from a lysogenic conversion event due to a filamentous bacteriophage, CTX. Two V. cholerae tyrosine recombinases that normally serve to resolve chromosome dimers, XerC and XerD, promote CTX integration by directly recombining the ssDNA genome of the phage with the dimer resolution site of either or both V. cholerae chromosomes. This smart mechanism renders the process irreversible. Many other filamentous vibriophages seem to attach to chromosome dimer resolution sites and participate in the rapid and continuous evolution of toxigenic V. cholerae strains. We analyzed the molecular mechanism of integration of VGJ, a representative of the largest family of these phages. We found that XerC and XerD promote the integration of VGJ into a specific chromosome dimer resolution site, and that the dsDNA replicative form of the phage is recombined. We show that XerC and XerD can promote excision of the integrated prophage, and that this participates in the production of new extrachromosomal copies of the phage genome. We further show how hybrid molecules harboring the concatenated genomes of CTX and VGJ can be produced efficiently. Finally, we discuss how the integration and excision mechanisms of VGJ can explain the origin of recent epidemic V. cholerae strains.
The EHEC generally have probably been around since the start of agriculture. They pre-date antibiotic use by humans. But the general abuse of antibiotics in meat animal intensive practices to improve yield is BAD BAD BAD. Use them and lose them. Perhaps animal only use might be justified is drugs that are useless in humans, but I doubt it. The quantities given to animals, where they are used are large. Use them for sick animals, yes. On the other had, IMHO indiscriminate or badly managed use in humans (as occurs in many developing countries) is also bad.
Remember also that the ability to mate is transmissible. In bacteria, sex can be infectious. Females turn into males when they have finished the conjugation ritual.
That’s quite an advantage for the genes involved in mating. They have evolved substantially different versions in different bugs. They can inject protein and DNA. In Agrobacterium they allow mating with plants. E. coli will even mate with a beer yeast if you let it. That is very uncivilized but completely natural
The mechanism(s) by which antibiotics in animal feed stimulate growth rate, increase body size, accelerate sexual maturity and increase efficiency of feed conversion to animal biomass remain unknown.
I think it is likely not due to the promotion of beneficial bacteria. No such bacteria have been identified and no plausible mechanism has been suggested for the effect. What those bacteria would do is unclear. Farm animals are fed ad lib, so if consuming more would stimulate growth, presumably they would.
One of my pet theories is that it is due to suppression of commensal ammonia oxidizing bacteria on the external surface which I have found are commensal on many organisms, including mammals. These bacteria set the basal NO/NOx level by oxidizing ammonia in sweat into NO and nitrite which is rapidly absorbed. The basal NO/NOx level is a global control parameter that sets things like androgen level. Low NO causes high androgen levels which stimulate growth of hair (in humans) that expand the niche where these bacteria grow (in humans). The P450 enzyme that is the rate limiting for androgen synthesis is inhibited by NO, so low NO causes more androgens.
The ammonia oxidizing bacteria are obligate autotrophs (which is I think why no one else has found them as commensals). Any mechanism for removing them will have the same effects. I think that by removing the commensal biofilm of ammonia oxidizing bacteria by bathing, humans are doing to themselves what antibiotics in animal feed do to farm animals; stimulate growth rate, increase body size, accelerate sexual maturity and increase efficiency of feed conversion to body mass. In 1850, the average of menarche was almost 17. Now it is maybe 12? Or less?
Look especially at figure 1. I think the loss of these bacteria do other things too.
German Strain has
EaggEC Virulence plasmid: – aatA-PCR: + (positive), – aggR-PCR: + (positive), – aap-PCR: + (positive)
Bill Marler has revealed the German out strain has the EAgg Plasmid which is decribed here:
Interdiscip Perspect Infect Dis. 2010; 2010: 254159
Published online 2010 March 11. doi: 10.1155/2010/254159.
Copyright © 2010 P. Kaur et al.
Enteroaggregative Escherichia coli: An Emerging Enteric Food Borne Pathogen
P. Kaur,, 2 A. Chakraborti, and A. Asea
We are dealing with an EAEC-like E. coli which also has the Shiga toxin 2 gene.
Geez. That is very cool informed speculation!
Yes, I know about this. I think it is easiest to fine antibiotic resistant strains in feedlots and hospitals.
But the issue is not antibiotic resistance but the lethal form of e.coli. Of course when the two go together that is worst case.
What about changes in feed practices and the impact on gut flora? Has feed shifted to less hay and silage and more starch/sugars, which I’d expect to change gut ecology in ruminants significantly.
This is a very impressive and intelligent discussion ! Thanks David !
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