Hantavirus may pose bigger zoonotic threat than we thought

The adorable host of a virus that causes your lungs to fill with fluid.

A small, innocuous looking virus with just three genome segments, causes one of the most deadly infections in the United States. Hantaviruses circulate worldwide causing either hemorrhagic fever with renal syndrome (HFRS) or, in the case of the North and South American strains, Hantavirus pulmonary syndrome (HPS). Famously recognized in 1993 in the Four Corners region of the U.S., Sin Nombre Virus, a strain of hantavirus, still infects at least a few people in the U.S. every year.

Hantaviruses are thought of as a virus people only get directly from rodents, which cannot be transmitted person-to-person. Infections result from exposure to contaminated excretions/secretions of rodents infected with the virus, though the rodents themselves show no signs of disease. These rodents also transmit the virus to each other.

Coevolution with hosts

While many species may be drivers for the evolution of another, the term coevolution is applied when two species influence each other so much that they are evolving together, where one undergoes genetic change the other responds with genetic change. They are undergoing speciation together. It was thought for a while that rodents were unharmed by the virus due to long, ongoing rodent-hantavirus coevolution. Significant phylogenetic congruities have been shown, for example, the phylogeny shown:

Screen Shot 2017-09-07 at 9.36.14 PM
Host species phylogeny on left, virus phylogeny on right, lines indicate which host virus infects.

New research might be indicating that’s not as true as we thought, phylogenetic analysis studies may be flawed, host range my be bigger, and rodent speciation doesn’t match up. While I’m not enough of a hantavirus or rodent expert to weigh in on this, certainly “whoa if true” to the coevolution theory.

Person-Person Transmission

In 1996, an outbreak of hantavirus in Argentina occurred, yet there was especially low rodent density and there was strong evidence for person-person transmission.

Then in 2011, a similarly unusually outbreak in Chile occurred. An Andes hantavirus, a close relative to the North American Sin Nombre virus (meaning “no name” as the native Americans), was shown to be transmitted person-to-person. In an outbreak of 5 human cases, symptoms developed in 2 household contacts and 2 healthcare workers after exposure to the first patient patient. Analysis of isolates from each patient supported person-person transmission for the all secondary-case patients.

Hantavirus found in human saliva

You might optimistically tell yourself that maybe this Andes hantavirus was a unique case. And maybe hantavirus was still really just a rodent disease that rarely spilled over to a person. But in Sweden in 2008, a Puumala hantavirus that causes hemorrhagic fever with renal syndrome (nephropathia epidemica) was found in human saliva of 10 patients. Whether or not this is actually a mode of transmission or not remains to be seen, but it does seem like hantaviruses are becoming more adept at infecting and transmitting between human hosts.

Climate change’s effect on hantavirus?

Hantaviruses frequently jump hosts and seem to circulate amongst bats, moles, shrews, and rodents, but climate change and human impact generally decreases rodent diversity. Intuitively you may assume hantaviruses would be less able to jump hosts as global warming/human impact goes on.


Perhaps colder areas will actually see a decrease in hantavirus outbreaks as a result of global warming, due to the expected decrease in vole/northern rodent species populations. Yet that doesn’t seem to be what’s happening. Hantavirus surveillance has indicated an INCREASE, not only in outbreaks, but in genetic diversity and abundance in rodent populations.

If climate change does end up resulting in low rodent densities, this may also present another hantavirus risk– providing selective pressure for the virus to change transmittance route.

deer mouse dusted with fluorescent powder to identify which mice got in most fights/matings thereby spreading more hantavirus. It was big, old mice.


  1. University of Utah. “Big, Old Mice Spread Deadly Hantavirus.” ScienceDaily. ScienceDaily, 9 January 2009.

2. Phylogeny and Origins of Hantaviruses Harbored by Bats, Insectivores, and Rodents. Wen-Ping Guo-Xian-Dan Lin-Wen Wang-Jun-Hua Tian-Mei-Li Cong-Hai-Lin Zhang-Miao-Ruo Wang-Run-Hong Zhou-Jian-Bo Wang-Ming-Hui Li-Jianguo Xu-Edward Holmes-Yong-Zhen Zhang – PLoS Pathogens – 2013

3. An Unusual Hantavirus Outbreak in Southern Argentina: Person-to-Person Transmission? Rachel Wells – Emerging Infectious Diseases – 1997

4. Hantavirus RNA in Saliva from Patients with Hemorrhagic Fever with Renal Syndrome. Lisa Pettersson-Jonas Klingström-Jonas Hardestam-Åke Lundkvist-Clas Ahlm-Magnus Evander – Emerging Infectious Diseases – 2008

5. Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011. Constanza Martinez-Valdebenito-Mario Calvo-Cecilia Vial-Rita Mansilla-Claudia Marco-R. Palma-Pablo Vial-Francisca Valdivieso-Gregory Mertz-Marcela Ferrés – Emerging Infectious Diseases – 2014



Salty Antarctic Lake Provides Clue to Viral Evolution

In the Vestfold Hills region of Antarctica, a team of researchers have discovered a unique method of genetic exchange happening in a deep lake—so salty it remains unfrozen down to minus 20 degrees. In it, lives members of Haloarchaea, a class of Euryarchaeota that thrive in high salt conditions. These extremophiles are able to thrive by having extremely high rates of horizontal gene transfer, swapping genes with other genera even, to more rapidly evolve. Despite the shockingly high rate of gene sharing, the lake still maintains distinct species with no one dominant species winning out. The lake is incredibly cold, providing very little energy, so the archaea in this area only produce about six generations a year because they have to metabolize and reproduce so slowly.

While people have been aware of the archaeal extremophiles there for some time, it was only recently that anyone noticed their plasmids.

Haloarchaea colonies

The team discovered plasmids in one strain that were not behaving like regular plasmids. Plasmids are pieces of DNA independent of the host genome which replicate independently and are kept around usually only if they have some beneficial gene to the organism (e.g. antibiotic resistance). What differentiates a plasmid from a virus is the method of transmitting genetic information.

For background, a plasmid typically relies cell-cell contact or “conjugation”–when a sex pilus of a bacterial cell containing the plasmid will combine with another bacterium to transfer the plasmid, or is picked up as naked DNA. Other horizontal gene transfer methods would be transduction (genetic transfer via a virus) or transformation (the collecting of naked DNA from the environment).

Viruses travel, encased in a protein coat, and rely on lysing or budding off their host cell and finding new cells to attach to and enter (or, in the case of retroviruses and lysogens, integrating in the host DNA and being activated later in any of that host’s progeny).

But these plasmids are acting like viruses. The pR1SE (plasmid) encodes proteins that go into the host membrane and allow the membrane to bud into vesicles containing plasmid DNA. These vesicles could then infect more of the archaeal species, plasmid-less members. The plasmids could then replicate themselves in their new host cell.

Besides this just being cool because it’s a way we’ve never seen before of transmitting DNA (and because anything involving archaea in extreme environments is cool), it also may be representative of some early stage of viral evolution.

Viral evolution is a hugely debated topic with no one really agreeing on how viruses came about, whether they evolved many times or once then diversified, which came first in the evolution of life etc., but this does seem to support the idea that at least some groups of viruses may have started as plasmids.

Some people think the obvious answer to viral evolution is gene reduction (a lot of giant virus fans), others think it’s gene addition (what this supports). I think the answer is gradually proving to be both—that viruses have evolved independently many times throughout history, and you could probably find at least a few examples to best support each major theory.


  1. Susanne Erdmann, Bernhard Tschitschko, Ling Zhong, Mark J. Raftery, Ricardo Cavicchioli. A plasmid from an Antarctic haloarchaeon uses specialized membrane vesicles to disseminate and infect plasmid-free cells. Nature Microbiology, 2017

2. High level of intergenera gene exchange shapes the evolution of haloarchaea in an isolated Antarctic lake. Ricardo Cavicchioli et al. PNAS. 2013

Echinoderms’ deviation from the universal code


The very strangeness of Echinodermata is partly responsible for the dedication that specialists in the group feel. We revel in their weirdness.
-Rich Mooi

Given that every biology student in the world has been introduced to the standard genetic code, and likely uses it frequently, it is kind of baffling that so few of us ever bother to think much about it. As a longtime lover of systematics/molecular evolution, the knowledge that the “universal genetic code” is not actually universal has always caused me some level of concern when imagining how scientists cope with such an issue or if they even cope with the issue at all.

Usually when you look this up you find a lot of “the code is essentially universal, only a few exceptions have been found” which would imply that maybe one or two extremely obscure microorganisms violated this rule slightly. But mammals mitochondria actually contains four out of 64 codons that do not match the universal code. Echinoderms, yeast, platyhelminth worms, all follow slightly different mitochondrial DNA codes and protozoan and some bacteria even follow different nuclear DNA codes (nuclear being the only DNA bacteria have).

While there are 64 codons, there are fewer than 64 tRNAs, which use an anticodon sequence to recognize a codon on mRNA and carry the appropriate amino acid at the other end. Different tRNAs with the various amino acids will sort of float in and out until the right one’s bound. The third position of the anticodon (the ‘wobble position’) however, binds very loosely to the DNA which is why the tRNA usually relies on recognizing the first two nucleotides. Some amino acids can have multiple tRNAs recognizing them but RNA modifications in the anticodon region of tRNAs can result in the evolution of a deviation to the universal genetic code. The echinoderm’s genetic code evolution is particularly intriguing which is hardly surprising given everything else about them.

A recent Nature paper shows an example of how this works in echinoderms. In echinoderm mitochondrial DNA, the codon AAA, which according to the “universal code” should code for a lysine, actually codes for an asparagine. Analyzing the tRNALys isolated from a sea urchin, they discovered a modified hydroxylated nucleoside; hydroxyl-N6-threonylcarbamoyladenosine. This modified nucleoside adjacent to the anticodon prevents the mt-tRNALys from misreading AAA as lysine, allowing AAA to code for an asparagine.

Mitochondria generally use a codon-anticodon pairing rule that allows unmodified uridine at the anticodon first position to pair with all four nucleotides at the third codon position. When an amino acid only has two codons corresponding to it, the G forms a base-pair with pyrimidine, and modified uridines (5-carboxymethylaminomethyl-uridine being a commonly heard modification to the wobble position base) can discriminate purines from pyrimidines. The presence of a pseudouridine in starfish mt-tRNAAsn in the middle of the anticodon allows the tRNA to decode the AAA codon more efficiently than the unmodified tRNA. Also interesting, the mt-tRNAs possessing anticodons similar to tRNAAsn, but which only decode two codons each (tRNAHis, tRNAAsp and tRNATyr) all possess unmodified U (position 35), further indicating pseudouridine (Ψ35) is important for decoding the three codons.

While certainly not all examples of a modified genetic code work quite this way, it’s intriguing to realize how something generally portrayed as being set in stone, is relatively labile and dynamic.

Given that systematics has favored mitochondrial DNA for many phylogenetic analyses, this could have an effect on the results if using an amino acid alignment or a distance matrix where each amino acid change is weighted a certain amount. You could imagine an alignment between mammals, echinoderms, and reptiles for example, where an AAA to an AAG would be a synonymous mutation (as in, not changing the protein) in mammals and reptiles, but a nonsynonymous mutation (changing the amino acid) in echinoderms, thus deserving a different score. AGA and AGG which both code Arginine in the ‘universal’ code, code for a stop codon in our mtDNA, while our nuclear DNA’s stop codon (UGA), codes a tryptophan. An AUA isoleucine in our nuclear DNA is read as a methionine in our mtDNA. There are likely many more “exceptions to the rule” that we have no idea exist.


  1. Hydroxylation of a conserved tRNA modification establishes non-universal genetic code in echinoderm mitochondria. Asuteka NagaoMitsuhiro OharaKenjyo MiyauchiShin-ichi YokoboriAkihiko YamagishiKimitsuna Watanabe Tsutomu Suzuki. Nature Structural & Molecular Biology (2017).

2. Tomita, K.Ueda, T. & Watanabe, K. The presence of pseudouridine in the anticodon alters the genetic code: a possible mechanism for assignment of the AAA lysine codon as asparagine in echinoderm mitochondriaNucleic Acids Res.2716831689 (1999).

Inducing cannibalism, “listening” for caterpillars- Plant defense


To protect themselves from hungry caterpillars, a tomato plant was shown to release chemicals that make it taste terrible to the caterpillars. The chemicals are so upsetting to the caterpillars that they decide to eat other caterpillars instead.

The research team who discovered this, sprayed the tomato plants with methyl jasmonate (which the plants produce in response to stress) to trigger defense mechanisms. The chemical acts as a signal, causing the plant to alter its chemistry, resulting in a plant that was much less appetizing to the caterpillars. The methyl jasmonate also can attract enemies of caterpillars like predators and parasitoids which will eat the herbivores.

So a tomato plant is being eaten by caterpillars and releases a chemical to warn the other plants and the other plants respond by releasing toxins that cause the caterpillars to become cannibalistic and eat each other instead of the plant. So the plants are communicating with one another and working together to alter the behavior of the caterpillar. The result is apparently larger stressed caterpillars nibbling on smaller caterpillars nearby causing some disgusting oozing.

What’s especially disturbing is the caterpillars seem to still revert to cannibalism even when other plant options are nearby. Why disperse farther when you could just eat a closer, unlucky smaller caterpillar I suppose.

Also congrats to that lucky undergrad who helped conduct this research and already got his name on a nature paper.

Listening for munching

Caterpillar chewing_free.jpg
Recording device next to munching caterpillar

In more amazing ways plants are able to ward off caterpillars, some plants seem to even respond to the vibrations of herbivory. the cabbage butterfly caterpillar munching the leaves an Arabidopsis plant results in the leaf moving up and down a miniscule amount. These vibrations were able to be recorded and played back to the plants so the scientists could compare plants left in silence to plants exposed to munching sounds (but no actual physical damage). The plants that were in the presence of the recording of chewing vibrations created an increased amount of mustard oil. Mustard oil is used as a defense against herbivores.

So just listening to the munching even with no caterpillars present somehow makes the plants better able to ward off future attacks.

The plants were exposed to other vibratory sounds none of which triggered any response. They have absolutely no idea how this works but it definitely provides more evidence that plants are amazingly adept to responding to all kinds of stimuli and information in the environment despite having no brains and being underestimated by basically everyone in science who is not a botanist.


  1. John Orrock, Brian Connolly, Anthony Kitchen. Induced defences in plants reduce herbivory by increasing cannibalism. Nature Ecology & Evolution, 2017
  2. Plants respond to leaf vibrations caused by insect herbivore chewing. M. Appel, R. B. Cocroft. July 2014

Phytoestrogens aid flightless parrot- Soy will still not give men breasts


Phytoestrogens are simply plant-derived xenoestrogens (mimics of estrogen). They’re abundant in legumes (soy, notably), but also present in many other plants. Despite their presence in certain plants being touted as scary, I’d say they’re pretty misunderstood.

Phytoestrogens help breeding success of kākāpō, the flightless nocturnal parrot

The darling flightless parrot of New Zealand has a struggling population partly because it only breeds once every few years. They seem to only breed during mast years (when plants produce a ton of edible fruit/seeds) and seek out fruit from the native rimu tree, which suggested the birds breeding success may rely on the presence of phytoestrogens found in the native plants. The hypothesis is that kākāpō don’t produce enough estrogen to make a fertile egg but the phytoestrogens act as supplements.qjjo1oz4sopgxokvcjww.jpg

The scientist conducting this study tested the native plants for estrogenic content and found high levels of phytoestrogens. They looked at the ligand binding region of the progesterone receptor, the androgen receptor, the estrogen receptor 1, and estrogen receptor 2 in four native parrot species, and non-native parrots and compared them with chicken receptors. They found that in most receptors there was more then 90% homology except in the estrogen 1 receptor. Parrot estrogen receptors are actually genetically different, containing an extra 8 amino acids in the hormone binding region, which changes the binding strength to estrogen.

Soy probably pretty good for you

Screen Shot 2017-07-30 at 11.12.05 AM.pngActive compounds of soy include isoflavones- daidzein, genistein, and glycitein. They act as phytoestrogens, a word which seems to frighten some people. A popular belief amongst anti-soy people is that men who ingest too much soy are going to re-enter puberty and turn into estrogen-filled feminized men (heaven forbid).

But this is not really what’s going on.

Phytoestrogens are structurally similar to estradiol so they have the ability to cause either estrogenic or antiestrogenic effects by blocking estrogen receptors. Phytoestrogens have weak estrogen activity in your body, so they may also bind weakly to estrogen receptors. They don’t displace estrogen, they supplement it.

Plants like soy have evolved phytoestrogens to protect from harmful microbes and to help form nitrogen-fixing root nodules.

So the expectation is that they act like antiestrogens in high estrogen concentration environments, and act like estrogen in low estrogen environments.

There are actually a lot of different estrogen receptors in the human body so the same chemical could be and agonist on one estrogen receptor type and an antagonist on another. So the phytoestrogens in plants could trigger an increase or decrease in endogenous estrogen through feedback loops.

It is almost certainly a serious oversimplification to say phytoestrogens are estrogen mimetics. Lots of compounds have partial agonist activity, meaning that at one concentration they are agonists and at a different concentration they are antagonists. It is possible they could affect the different receptors differently.

Reasons to even get excited over Phytoestrogens

Certain hormonal cancer (uterine, prostate, breast etc.) risks could possibly be lowered with phytoestrogen consumption. If they do actually compete with and block estrogen (an antagonist) at estrogen receptors in the breasts, cervix, or uterus, or if they depress estrogen production, they could tend to inhibit estrogen dependent tumors.


Phytoestrogens may even provide some sort of benefit to women undergoing menopause and experiencing hot flashes, and post-menopausal women at risk for developing osteoporosis and issues in cognitive function which can sometimes be experienced due to dramatic hormone changes.

If phytoestrogens are agonists at estrogen receptors on osteoblasts and osteoclasts they will help reduce osteoporosis. These estrogen receptors are quite different from the receptors on breast tissue.

From a meta analysis on the effects of isoflavones on bone mineral density in menopausal women: “Isoflavone intervention significantly attenuates bone loss of the spine in menopausal women. These favorable effects become more significant when more than 90 mg/day of isoflavones are consumed. And soy isoflavone consumption for 6 months can be enough to exert beneficial effects on bone in menopausal women.”

Soy phytoestrogens are associated with much less negative effects than synthetic endocrine disruptors. And while results of most of these soy studies are dubious—varying with age, level of consumption, and the composition of the individual’s intestinal microflora, soy studies are just as well supported as pretty much any other “eat/drink more of (vegetable, tea, “superfood” etc) and (some health benefit) happens” claims.

While most people tend to be skeptical of simply ingesting a plant and deriving benefits (especially when they are comparing the plant to the highly powerful and concentrated drugs we’ve developed), underestimating and understudying plants has brought about, and continues to bring about, death and illness to plenty of people. So maybe it provides small benefits, but at the very least research does seem to have debunked the myth that soy is dangerous for people.

Constituents of soy if you’re still worried



  • Protein
  • Oil- large amounts of polyunsaturated fatty acids (i.e. linoleic acid (omega 3))
  • Carbohydrates
  • Vitamins and minerals- K, P, Ca, Mg, Fe, B-Vitamins, antioxidants
  • Isoflavones
  • Phytosterols– Disogenin –sterol- is converted to progesterone in body
  • Phospholipids
  • Saponins*- being looked at especially
  • Ferritins- Soybean is a good source of iron
  • Phytic acid
  • Glyceollins- antiestrogen activity
  • Lunasin- peptide


  1. Unique oestrogen receptor ligand-binding domain sequence of native parrots: a possible link between phytoestrogens and breeding success. Catherine E. J. Davis A , Adrian H. Bibby A , Kevin M. Buckley A , Kenneth P. McNatty A and Janet L. Pitman. 11 July 2017.
  2. 2014 Jul 7. Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis. Cheng PF1, Chen JJ, Zhou XY, Ren YF, Huang W, Zhou JJ, Xie P.
  3. 2003 Jan-Feb. Effects of soy and other natural products on LDL:HDL ratio and other lipid parameters: a literature review. Hermansen K1, Dinesen B, Hoie LH, Morgenstern E, Gruenwald J. .
  4. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. Myung SK, Ju W, Choi HJ, Kim SC; Korean Meta-Analysis (KORMA) Study Group.
  5. Soy intake and cancer risk: a review of the in vitro and in vivo data. Messina MJ1, Persky V, Setchell KD, Barnes S.
  6. 2014 May 28. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: A systematic review. Thomas Ismail, Taylor-Swanson Cray, Schnall, Mitchell, Woods
  7. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Hamilton-Reeves JM1, Vazquez G, Duval SJ, Phipps WR, Kurzer MS, Messina MJ.
  8. Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Ma DF1, Qin LQ, Wang PY, Katoh R.
  9. Soy isoflavones for osteoporosis: an evidence-based approach. Taku K1, Melby MK, Nishi N, Omori T, Kurzer MS.

Platypus venom- weird and unique, as expected


“Do you think God gets stoned? I think so — look at the platypus.”

-Robin Williams

Venom isn’t very special in the animal kingdom, but our anthropocentric mindsets tend to focus more on large mammals than anything else, so to us it seems pretty mystical. Only a dozen or so mammals deliver venom, almost all of which deliver it via a bite for defense or predation. The platypus is unique in that it is so far the only animal known to use venom for a purpose other than defense or predation.

Only the male platypus has venom. And the male platypus only seems to have potent venom seasonally. The season when they have a lot of venom is unsurprisingly mating season, as the males actually use their venom, injected via venomous spurs on their hind legs, for intraspecific competition with other platypus males to keep territories and mates. While technically the echidna has venom, it can’t erect it’s spurs, and simply excretes a milky secretion.

platypus-spur-png.pngTheir venom, though nonlethal, causes excruciating pain for hours or days and is essentially nonresponsive to morphine. Only nerve-blocking agents (or antivenom) can provide relief.

A 2010 study found 83 peptides in platypus venom, many of which resemble venom genes from snakes, sea stars, and spiders. The platypus and reptiles have independently co-opted the same genes for venom usage making the platypus venom a cool example of molecular convergent evolution.

And just so the monotremes can continue to follow their pattern of general nonconformity and being surprisingly different from each other, the echidna venom gland transcriptome looks very different from the platypus one. You can read this post on their weird sex chromosomes for more.

The venom induces Ca2+ influx in cells, which results in neurotransmitter release. Defensin-Like peptides (defensins being immune proteins that usually defend the host from microbes), C-type natriuretic peptides (OvCNPs), nerve growth factor (OvNGF), and hyaluronidase have also been found. These peptides cause muscle relaxation, inflammation by promoting histamine release, and form ion channels in the lipid membranes of cells. The venom also contains a D-amino acid (as opposed to just all L-amino acids, which is the isomer previously thought to be the only conformation manufactured by cells).

First venomous animals were mammals
Artist interpretation of Euchambersia mirabilis

The platypus having venom and laying eggs isn’t even that weird, as it seems to be that that was the norm for the ancestors of mammals. Euchambersia mirabilis, a therocephalian therapsid from the end of the Permian (~255 mya), which were some of the “almost-mammals” (the term “mammal-like reptile” is horribly outdated and silly but for some reason people still use it), was determined to have venom glands. Venom glands which appeared way before snakes and lizards evolved them, and actually millions of years before any snakes even existed.

bk9781849736633-00001-f1_hi-resSo while venom in mammals is very rare now, it may actually be an ancestral characteristic. Venom relatively expensive to have as it requires some method of injection into another animal, a gland, and then the making of proteins. It’s also suspected to be expensive because the loss of venom in animals that are no longer under pressure to produce any, is very common. Venom has a weak phylogenetic signal—similar types of venom are not necessarily found near each other on a phylogenetic tree, so genetically it seems not very “difficult” for various venoms to arise.

Monotreme venom as diabetes treatment?

The hormone, glucagon-like peptide-1 (GLP-1), is secreted in the gut, stimulating the release of insulin to lower blood glucose. But GLP-1 typically degrades within minutes in humans.

People with type 2 diabetes can’t maintain a normal blood sugar balance, but maybe they could if they had a less rapidly degrading GLP-1.

However in the platypus, there’s conflicting functions of the GLP-1. Not only is it a regulator of blood glucose in the gut, it is also in their venom. This conflict between the two different functions has resulted in the evolution of a dramatically changed GLP-1 system. GLP-1 in monotremes is resistant to the rapid degradation that occurs in other animals, and degrades by a completely different mechanism.

GLP-1 and diabetes relationship

The function of GLP-1 in the venom seems to have resulted in the evolution of a stable form of GLP-1 in monotremes. Stable GLP-1 molecules can potentially be used as a type 2 diabetes treatment.

Both platypus and echidnas have evolved the same long-lasting form of the hormone GLP-1 despite echidnas not having spurs.



  1. Kita, Masaki, David Stc. Black, Osamu Ohno, Kaoru Yamada, Hideo Kigoshi, and Daisuke Uemura. “Duck-Billed Platypus Venom Peptides Induce Ca2 Influx in Neuroblastoma Cells.” Journal of the American Chemical Society50 (2009)
  2. Enkhjargal Tsend-Ayush, Chuan He, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank Grutzner. Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions. Scientific Reports, 2016
  3. Julien Benoit, Luke A. Norton, Paul R. Manger, Bruce S. Rubidge. Reappraisal of the envenoming capacity of Euchambersia mirabilis (Therapsida, Therocephalia) using μCT-scanning techniques. PLOS ONE, 2017

Cholera- it’s all about the phage


If, like me, you’ve been reading about the unusually horrific outbreak of cholera in Yemen, you may be wondering how it got so bad. While an understanding of ecology is central to fighting any disease, if feels especially important when discussing cholera, as the current Yemen outbreak is being almost entirely blamed on war resulting in collapsing infrastructure resulting in millions of people losing access to clean drinking water. On top of that, the malnutrition of many children in the area results in them being more susceptible to Vibrio infection.

To add to that, access to rehydration therapy (the common treatment for cholera when intravenous fluids and antibiotics aren’t an option) is low, and the vaccine campaign has been dropped with the justification being that the limited amounts of vaccine would not be as effective in Yemen as they would in areas where less people are infected.

The varieties of Vibrio

The most important vibrio species to human disease are Vibrio parahaemolyticus, Vibrio vulnificus, and Vibrio cholerae. Vibrio species have flagella and pili which are important virulence factors–notably the toxin co-regulated pilus. The cell walls of Vibrio contain lipopolysaccharides consisting of lipid A (endotoxin), core polysaccharide, and an O polysaccharide side chain. Vibrio can then be divided into serogroups based on this O polysaccharide (200 serogroups in V. cholerae’s case).

V. cholerae O1 and V. cholerae O139 both produce cholera toxin (which causes a rise in cAMP resulting in the cell losing nutrients, which is why you not only need tons of water, but also need to replenish lost electrolytes). These are the serogroups associated with cholera epidemics. Many strains of V. cholerae do not have this toxin and do not cause epidemics though they may still cause illness.

The O1 serogroup is further subdivided into three serotypes: Inaba, Ogawa, and Hikojima. There are then two “biotypes” of V. cholera O1: Classical and El Tor. These biotypes can be further subdivided but let’s just stop here.

The cholera that were famous for killing lots of people in the 1800s were all of the Classical type. The cholera that is responsible for today’s pandemic is of the El Tor biotype.

The CTXφ phage

V. cholerae secretes cholera toxin. This is the toxin that causes the “rice-water” stool (not diarrhea really, as it’s just mucus and water), resulting in dehydration of the host. Colonization of the small intestine required the toxin co-regulated pilus (coded by the vibrio pathogenicity island).PMC3282888_TOMICROJ-6-14_F2.png

The genes for cholera toxin are not in the Vibrio genome unless the bacteria has been infected by a CTXphi (CTXφ) filamentous phage, which inserts it’s genome into the V. cholerae genome. The CTXφ can transmit cholera toxin genes from one V. cholerae sstrain to another (via horizontal gene transfer).

Infectious CTXφ particles are produced when V. cholerae infects humans. Phages are then secreted from the infected bacteria without lysing the cell.

Seasonal epidemics inversely correlated with environmental cholera phage presence

Cholera seasons usually make sense as they tend to coincide with monsoon season. But perhaps less obvious (or totally obvious if you’re into viruses) cholera phages have a very dramatic influence on seasonality.

The presence of viruses infecting V. cholerae O1 or O139 inversely correlates with the occurrence of viable V. cholerae in the environment and the number of cholera cases. Both epidemic and nonepidemic serogroups have been shown to sometimes carry lysogenic phages which reproduce and kill epidemic strains. Lysogenic phages integrate into the genome so it replicates with every reproduction of the bacteria

One common O1 phage can use several V. cholerae non-O1/non-O139 strains as alternative hosts.

Having alternative hosts present combined with the lysogenic V. cholerae strains can result in a cholera phage “bloom,” thus lowering the transmission of phage-sensitive, more virulent cholerae strains.

Screen Shot 2017-07-13 at 11.06.58 PM
Concentration of lytic vibriophages in the aquatic environment of Dhaka, Bangladesh, and the estimated number of cholera cases. From Faruque et al 2004.
Phage and Vibrio waves controlling epidemics

 Cholera outbreaks occur in waves with different serogroups dominating at different times.

The absence of one phage specific for one cholerae type provides an opportunity for that serogroup to begin the seasonal epidemic. However, the phages for that serotype will eventually amplify in the environment and attack this serogroup, ending that epidemic.

A different cholerae serogroup would then be resistant to that first phage or carry it as a prophage in the genome—so it isn’t killing that bacteria. A second epidemic wave from the new dominating serogroup can now occur until phages specific to this new serotype bloom, thus ending the epidemic.

Some serotypes will be resistant to all the phages that were killing the virulent phages in the environment, and these serotypes will occupy the interepidemic periods. These strains usually lack typical virulence factors that would make them particularly good pathogens, but are instead more environmentally adapted than the other more virulent strains.

These resistant serotypes may ALSO harbor prophages—phages integrated in the genome—which kill virulent serogroups and may pick up virulence factors via horizontal gene transfer.
If this happens, new serotypes that were previously not very virulent may emerge as the new epidemic serotype.

Self-limiting seasonal epidemic also probably caused by phage

A naturally occurring lytic phage, JSF4 (lytic meaning it simply lyses the cell), infects and kills Vibrio that are sensitive to it.

In a study from 2005, it was shown that the peak of cholera season was preceded by a peak in V. cholerae presence which was then followed with a peak in JSF4 phage presence as the epidemic ended. JSF4 phages would then also be excreted in the diarrhea of sick cholera patients. So the patients at the end of the epidemic end up ingesting both a lot of V. cholerae as well as JSF4 phage which kills the bacteria. The increase of phage results in the decrease of V. cholerae and the epidemic ends.

This is likely why outbreaks are self-limiting.

V. cholerae O139 spread by turtles

Screen Shot 2017-07-14 at 12.56.28 AM.pngWhile O1 causes the majority of outbreaks, O139 is confined to Southeast Asia. Recently however, it’s been discovered that soft-shelled turtles in China are big carriers of O139. While a lot of aquatic animals spread cholera, the soft-shelled turtles have been definitively linked to human disease and make excellent hosts as they are unaffected by the bacteria which clings to many of their surfaces and intestines. These turtles are then consumed by people, to spread more cholera to new unsuspecting hosts. If turtles being cute wasn’t a good enough reason to stop eating them, maybe this is?


Jiazheng Wang, Meiying Yan, He Gao, Xin Lu, Biao Kan. Colonization of Vibrio cholerae on the Soft-shelled Turtle. Applied and Environmental Microbiology, 2017

Faruque, S. M., I. B. Naser, M. J. Islam, A. S. G. Faruque, A. N. Ghosh, G. B. Nair, D. A. Sack, and J. J. Mekalanos. “Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages.” Proceedings of the National Academy of Sciences 102.5 (2005)

Faruque, S. M., M. J. Islam, Q. S. Ahmad, A. S. G. Faruque, D. A. Sack, G. B. Nair, and J. J. Mekalanos. “Self-limiting nature of seasonal cholera epidemics: Role of host-mediated amplification of phage.” Proceedings of the National Academy of Sciences 102.17 (2005)

Murray, Patrick R., Ken S. Rosenthal, and Michael A. Pfaller. Medical microbiology. Philadelphia, PA: Mosby/Elsevier, 2016.