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TWiM regularly receives listener email with corrections, comments, suggestions for show topics, requests for clarification, and additional information. A selection of these is archived on this page.
TWiM & TWiV team,
Keep up the excellent work! I am an electronics engineer who has never studied biological sciences, but now in my 50's, I find your podcasts fascinating. I listen to episodes while working out - a good combination of mental & physical exercise ... thank you!
If you haven't already, please read this article in Scientific American, Dec 2013:
What I found interesting:
(1) Fungi have much larger genomes than bacteria or viruses, and this combined with sexual reproduction, gives them a larger arsenal for rapid adaptation.
(2) In the wild, the biggest predators for this fungus are amoebas, therefore it has developed protection mechanisms. If fungus ends up in humans, marcophages look very much like amoebas, and the fungus hitches a ride inside the macrophage, protected from the immune system until it can replicate and do damage.
Maybe you can do a show on virulent fungi? TWiF? Elio should be interested …
Here's an article which describes a TB drug that can be tweaked to target multiple disease-causing bacteria, and also ward off resistance by targeting multiple pathways in organisms.
[here is the paper: http://www.ncbi.nlm.nih.gov/pubmed/24568559]
I have a suggestion for a slightly out-of-the-way article that would be interesting to hear you analyze. I may be wrong but this article seems a little "primitive" and almost designed to continue an "alien origin" scenario. Despite that, this appears to be a genuine phenomenon in need of some specificity.
Personally, I'd love to learn that it is a stratospheric life form that got swept down to earth but I suspect that it is much more likely to be an oceanic life form swept up by a typhoon.
"Morphological and Molecular Analysis Calls for a Reappraisal of the Red Rain Cells of Kerala", Rajkumar Ganagappa, Mark J. Burchell, Stuart I Hogg, Current Microbiology (2014) 68: 192-198.
Regarding episode 72, I have to confess that it was one of those episodes that went, mostly, right over my head. Fortunately, I was saved by a listener's question regarding using beer as a vaccine medium against yeast infections. At least I know a little about beer.
First of all, I don't have any set answers for your querent. I do have some information that might help set the stage.
Yeasts are indeed used in the production of beer but comparing the basic beer yeast (Saccharomyces) with an infectious yeast like, say, Candida is lot like comparing the stomping power of the hyrax versus an elephant. They may be related but they're different beasts. That said, it might be possible and even practical to infect a beer wort with infectious yeasts and have them proliferate. If you could figure out some way to engineer a non-infectious version of that yeast, then I suppose that it might be possible to prime the immune system against infectious strains of that yeast. My guess is that the process is a lot tricker than with, say, polio or people would already be doing it. In addition, it would likely change the taste of the beer which might or might not be a good thing. Fermentation with non-Saccharomyces yeasts is being studied and does have some beneficial properties.
Then there is the question of actually getting the non-infectious infectious yeast or some significant immune-response-inducing part of it into the final product. If you lysed the yeasts and the appropriate vaccinating portions were soluble and smaller than the filter size, then that could work if you didn't denature it with the heating process first.
There might, however, be a simpler way. Europeans and Americans prefer their beer clear and non-yeasty so they heat it up and filter it. There is, however, a class of ancient beers called opaque or sour beers. These are simple beers which are not filtered (hence both yeasty and carbohydraty - a full meal at lunch time). They are also produced by the combined actions of yeasts and lactic acid bacteria (hence the sourness). For the most part, these beer are living beers, made in the home, and drunk within a day or two. They are best-known in Africa.
If the non-infectious infectious yeast could be supplied in a dormant state able to withstand, for instance, the hot african sun, (perhaps in a spray-dried sugar-yeast mix) then the yeast could be added to this sour beer, proliferate, and be drunk live to induce the immune response. Any taste differences would be much less noticeable in this product and it would fit in well and easily with the daily food consumption of some areas of the world.
Of course, if you could get it into a dormant state in sugar, then it might just be easier to distribute it in lollipops.
Interesting idea that probably won't work but it does lead to some interesting possibilities for integrating other medicinal microbes into diets.
Heard you mention that you had a competitor by the name of Goggles Optional, so being obsessive about science, I looked them up and tried listening to a few of their podcasts. It's reminiscent of TWIS and no real competition to your in depth science podcasting! Actually, it's a bit aggravating.
Hi, I have some comments regarding your dislike of some choice of words in the microbiology and molecular fields. This discussion should be able to fit both twiv and twim.
First you say that the term prokaryote is wrong, but i think the meaning that it has widely attached to the word is wrong. Usually people think of the word to mean without nucleus, and usually we think of these organisms coming before the eukaryotes (that is another discussion altogether) but i don't find this is correct.
there are two stems pre- and pro- , both of them can be meant to mean before, but in a different way. pre- would mean to me something that happens before the appearance of anything, so cells that appeared before eukaryotes would be prekaryotes. Now, prokaryote would mean to me protokaryote, which people may have chosen to shorten to prokaryote. This fits best with the description of these organisms, since they have a nucleiod or protonucleus, some sort of organization that is not quite a nucleus but it is there. so I think prokaryote fits best if it is explained right.
The other is your dislike to the expression "a protein is expressed in the X", you say that we shouldn't say this but instead the protein is translated and that a only a gene can be expressed, and i think this is wrong as well. A gene is transcribed, a protein is translated. What i mean by wrong is that the word expressed according to (http://dictionary.reference.com/browse/express) can signify to manifest. Following this, a gene is expressed when the DNA is copied and the specific bases of the gene are put together, an mRNA is expressed when the gene is transcribed by RNAPol, and a protein can be expressed when it is translated and when it has reached its final destination.
One other comment is how we are thought about bacteria. It is regarding the fact that bacteria are thought of archaic life forms, and while the first lifeforms might have resembled more single celled organisms, both the lineage that gave rise to humans is as old as that of bacteria since we should have the same primordial ancestor, unless there were independent primordial life forms formations. Everyone should be taught that any extant organism is as "modern" as any since all organisms have to adapt to the changing and current environment. So we can say that current bacteria are the best expression of their lineage, and not that being unicellular organisms they chose to not continue to innovate biologically.
A latest topic of discussion has been the state of science, and it occurred to me that while most people in science say that cutting down the number of PhDs and restructuring, it seems contradictory the fact that there are very active programs of highschoolers and minorities into science with the excuse that we need more scientists, what are your thoughts on this?
Thanks for your discussions, I'm always looking forward for each episode of the Twimvps and also urban agriculture.
Dear TWIM hosts,
I enjoyed episode 76, "Genetic biopixels and a pathogenic sweet tooth". I really enjoyed hearing about the course that Dr. Schaechter teaches and in particular the work his students did in developing the biosensor. I would like to recommend a couple of papers that a classmate in my differential equations class told me about. They can be found at Biomed Central and are open source which is great. The first is "Solving a Hamiltonian Path Problem with a bacterial computer", Jordan Baumgardner et al, J Biol. Engineering 2009, 3:11. The second was also published in the same journal, "Engineering bacteria to solve the Burnt Pancake Problem", Karmella A. Haynes et al, J. Biol. Engineering 2008,2:8.
A Hamiltonian Path Problem involves finding a route in a directed graph that starts at a node ( the beginning node) and visits all of the nodes in the graph exactly one time. Companies like FedEx solve these kinds of problems daily in determining the most economical and efficient routes for their delivery persons. Solutions to these types of problems are very complex and computationally intensive. The authors used E. coli that contained a Hin/hixC recombination system from S. typhimurium to randomly shuffle DNA segments as the computing system. They represented nodes in the graph as linked halves of two different genes encoding red or green fluorescent proteins. The bacterial populations displayed phenotypes that reflected random ordering of the edges of the graph. A Hamiltonian path was reported by fluorescing both red and green, resulting in yellow colonies. The Burnt Pancake Problem involves sorting a stack of distinct objects into proper order and orientation using the minimum number of manipulations. This paper describes a proof-of-concept of "in vivo" computation. volunteer
I enjoy so much listening to all of the TWIV, TWIM and TWIP podcasts. Since I've been working on my math degree I don't really have anyone to talk biology, biochemistry, etc with and I miss it. I'm down to the last 2 course before I'm finished, "Real Analysis" and "Probability". I'm hoping that I can find a lab to volunteer to help out in and I've been looking but so far no one has been too keen on having a 70 year old guy hanging out in the lab. Oh well, I have had been able to take some interesting breadth classes and just finished BIoInformatics. It was a trip to actually do sequence analysis and construct heat maps and run blasts! Anyone working on a machine to reverse aging I'm a willing volunteer.
Weather in Orange CA this week has been hot and dry. Today was 98 F, 37 C, 4% humidity, dew point 4 F, winds 20 - 30 mph. We have more of the same predicted for tomorrow and into the weekend. To windy to sail, to hot to just lay around at the beach, and with the winds the surf sucks. So good time to hole up inside in the air-conditioning and enjoy some episodes of TWIM.
Dr. Robert Kelley (Bob)
Dear TWiM team,
I am currently studying for my Biology degree second year exams in the UK and have listened to my first TWiM podcast today. Id like to quickly thank you as the zombie plant topic made perfect outside reading for my plant exam in a few days! I’m about to tackle the paper now.
I will continue listening for more interesting topics!
Thanks so much,
I'm giving a final exam right now, then flying out to Boston for ASMCUE/ASM. Maybe I will see some of you there!
I adore this concept of parasites/pathogens/symbionts altering the behavior of their hosts. Sounds like you all do, too!
Elio had some interesting ideas about viruses and behavior.
I know that folks are short on time, but the SF writer David Brin has an old story about this, called "The Giving Plague." It's online here:
Here you have a virus that causes altruistic behavior! It reminds me of the story (I'm sure it's not true) about the fellow who survives rabies. After he recovers, he is asked why he tried to bite people. He thinks for a moment and replies "It seemed like a good idea at the time."
Even though the virology may make you wince (I love SF, but the authors sometimes...well...play a little fast and loose with the actual world of science), I think you and your readers might enjoy Dave Brin's story.
I will be teaching a freshman writing course on symbioses and parasitism this Fall at my small liberal arts college, and you can rest assured I will be discussing this and related issues with them (including TWiP!). Happy for any suggestions or assistance out there!
As always, I so enjoy listening to your podcasts.
Mark O. Martin, Ph.D.
Department of Biology
University of Puget Sound
Dear Drs. Racaniello, Schaecter and Schmidt,
Thanks for the great episode on swabbing the environment around hospitals to check for prevalence of antibiotic resistant microbes. The idea of resistance spreading out from health care facilities seems very intuitive after hearing about it but I'd never thought of this before. It got me thinking about the number of other livestock farmers I know who have a family member that works in health care as well as helping on the farm. Could this be leading to increases in antibiotic resistant organisms in livestock or obviously vice versa?
I also found the practice of using antibiograms interesting. I had not known how doctors make decisions on which first course antibiotics to use. I will have to ask my veterinarian friends if there is an antibiogram equivalent in animal medicine.
Thanks again for another great episode and also for the TWIV bump for our AgSciToday podcast. It was much appreciated by Steph and I. Hope that nice late spring early summer weather has rolled in where you all are and that you have a few chances to get out and enjoy it. It's a balmy 18 C here in MN and finally not raining for once although it did just rain 1.25" the other day so we were due some decent weather. I'll also add a planting progress report despite that not being a typical feature on the show - we have around 60% of our hay fields seeded, 0% of our corn and 0% of our pasture ground interseeded. Usually those numbers would all be around 100% at this time. It's been another wet spring to say the least.
After listening to the second portion of TWiM 78, talking about the presence of gram-negative nosocomials around Brooklyn, I noticed a several people wearing scrubs while at lunch near a hospital in Houston, TX. Then a thought occured to me; disease! Disease everywhere! Might part of the problem, if these microbes are moving out from the hospital, be that they're carried from a day's worn clothes? I realize I'm asking to speculate, but think this might be a good consideration for hospital policy. Houston is currently 27 C at a low 50% humidity.
P.S. I finished my sandwich. It was a pastrami ruben.
"Ideas" with Paul Kennedy on the Canadian Broadcast Corp site recently ran a 54 min program about invasive species that included a short reference to rock snot. At the link find the title, "Bioinvasion: Attack of the Alien Species!," right-click (here or there) "Download Bioinvasion: Attack of the Alien Species!" to download it. I thought it, along with Prof Schmidt's comment about furry teeth, are a good intro to any program for kids about bio-films.
You have spoken before on TWiM about the potential risks of triclosan-resistant pathogens developing through its over use.
A recent open-access article from the the University of Michigan, published in mBio, looks like it may be worth a mention. The researchers conducted a study that examined the nasal passages of healthy adults, 41% of those sampled had traces of triclosan in their nasal secretions and the presence of triclosan in the secretions also correlated positively with nasal colonization by Staphylococcus aureus.
When grown in the presence of triclosan, Staphylococcus aureus was was found to be better able to attach to human proteins.
Additional experiments found that that rats exposed to triclosan were also more susceptible to nasal colonization by Staphylococcus aureus.
Del writes: (re: episode 77)
I was looking forward to this discussion, after hearing you hint about it in a previous podcast. As a practicing ID doc, I have been fascinated by the difference in pain induced by cellulitis from presumed or proven Staph or Strep infections. I see some patients whose pain resolves in a day or so after antibiotics, and some fewer patients who have a much more protracted course of pain, with tenderness to minimal touch or change in position. I have suspected that different isolates produce different toxins to explain these clinical differences, as my clinical judgement and experience argues that patient personality differences or 'pain thresholds' are simply not enough explanation for the variation I see. It also seems to "be there, or not be there," more distinctly than a simple continuum would explain. I am grateful for the basic science work being done in the field at present, and for your discussion.
Thanks to you all for the work you put into this podcast. I am learning every week, and finding connections in areas I would have never before considered.
All the best,
Del DeHart MD FACP
Associate Professor of Medicine
Michigan State University
I realize that this is a bit behind the times but I have two questions related to beta-lactamase (hope I got that right) form episode 6 - "Antibacterial Therapy with Bacteriophage".
1) We all know that the proliferation of bacterial resistance to antibiotics has a direct influence on infection recovery in humans and animals. What I'm pretty sure most people forget is that most antibiotics began their "careers" as part of microbial defense systems. Are you folks aware of any studies looking at the effects of increasing antibiotic resistance in environmental microbiomes? I would think that this human-induced change has got to be skewing microbial populations and interactions. Indeed, I'm having trouble even imagining what the impacts on the microbial and, therefore macrobial world might be.
2) During your discussion of beta-lactamase gene development in the environment, I thought of a possible counter that might help us continue to use beta-lactam antibiotics a little longer. Are you aware of any groups who are researching anti-beta-lactamase drugs that could be added to antibiotics allowing the beta-lactams to retain some effectiveness against resistant microbes? If someone developed a low-toxicity drug that had a significantly higher and, one would like, non-reversible affinity for beta-lactamase than beta-lactam. then one could, presumably, administer it along with beta-lactam and it would inactivate the beta-lactamase while leaving the beta-lactam free to do it's work. Such a system probably wouldn't be effective within a microbe but it should be effective for running interference at cell membranes.
Thanks for the interesting shows,
Dr. Schmidt's viral illness would be quite serious if there was consolidation as was asserted.
Consolidation refers to the gross characteristics of the lung when it turns from fluffy and pliant into solid as the air spaces become filled with cellular and proteinaceous exudates in pneumonias. Bad enough with bacteria and the antibiotic resistance problem; if it is a viral pneumonia, the treatment modalities are mostly supportive care.
It's been found that nasal carriage of Staphylococcus aureus is associated with increased risk of infection due to dispersal of SA from the nose while breathing and by nose-picking and not washing your hands. Some individuals are colonized with SA and are more prone to infection. Now there's a lot of research on how best to decolonize the nose of SA, because it survives antibiotics and quickly recolonizes the body. Mupirocin is typically used, but results are not good and resistance is likely. Seems to me that the aim of decolonization is stupid, since it is impossible to kill every last cell in and on the body, and even if you could there's plenty more in an individual's environment (which can survive for months on surfaces) to recolonize them anyway. Surely a better aim is to find out why some people do not become colonized and reproduce whatever they have in colonized people. Presumably, there's something about uncolonized peoples' immune systems and/or microbiomes which makes it hard for SA to become a problem. Maybe it's like the problems some people have with gut bacteria, where gut bacteria (shit) transplants have been shown to be effective. Maybe similar transplants of bacteria from the skin and/or nose of uncolonized individuals would be as effective for SA depopulation? It's a revolting idea, but no more disgusting than a poo-transplant!
Didn't recognize "Speak friend and enter!" and "NIN" ?!? What kind of barbarians do you invite on this show?!
Just kidding. TWIM # 73 was another amazing and wonderful podcast. I am only a geologist, so I can sometimes only vaguely hum along with yours, Michele's, and Michael's biochemistry arias. Nonetheless, TWIM is one of my favorite podcasts. When I listen on my walking commute from my home to my office in Seattle, I arrive smarter!. And grateful. I am always grateful after listening. Thank you!
Hello Twim team,
After reading the Pasteur lecture.
It seems that the idea of using the Pseudomonas aer, "coal & septicemia" came from a demonstration that the "bactericidie" in the blood from animal with anthrax ("sang charbonneux") was the only origin of the disease.
It was a point of contention in the fight against the last supporters of the spontaneous generation.
When use the "sang charbonneux" from death animals collected at a rendering facility was shown to kill rabbit, but without the presence of the bactericidie in the rabbit blood.
Pasteur was able to demonstrate that was due to contamination of the corps blood between the time of death & the collection, by the "virions" causing "septicemie". And that's was causing the destruction of the "coal virulence" (virulence charbonneuse). For him it was of therapeutic interest, but it seems he has never used it on human (only on guineapigs).
He has developed instead the vaccination against anthrax by selection of an attenuated variant.
By the way fun coincidence with Michael remarque to Elio about the LON & E coli turning to snakes.
In the same lecture Pasteur also observed that outside of the blood in septicemia killed guinea pigs, the bactericidies form long snake like filament "creeping, sinuous, and separating the blood cells as a snake separate the grass in the bushes".
I have never been as excited about a podcast as I was when I saw the title of the latest episode of TWIM (#51, Cave science with Hazel Barton), and it definitely did not disappoint! I listened to it twice right away. I'm trying to specialize in metagenomics, and I love caves and caving. If someone had asked me to design my dream TWIM, it would have been exactly like this. I had actually thought about suggesting the antibiotic resistance in cave microbes -paper for discussion, but I didn't think anyone else would find it interesting - probably because I come from a country with no proper caves, where you only get blank stares when you mention caving. Thank you so much for this episode!
I also have a question. Dr. Barton mentioned they have tried to do 454 sequencing, but apparently they haven't published anything about that yet? Do any of you know of any sequencing-based cave microbiome papers, particularly about "normal" karst caves? I've been unable to find anything on my own.
Thank you once more for the most awesome podcast episode ever,
(your subway-driving fan from Finland)
[I asked Hazel. She wrote:]
Yeah, unfortunately we've done a ton, but the papers aren't done.
Here's some good references though:
Making a living while starving in the dark: metagenomic insights into the energy dynamics of a carbonate cave. Ortiz et al, ISME J, 2013 (1-14).
Life in the dark: metagenomic evidence that a microbial slime community is driven by inorganic nitrogen metabolism. Tetu et al, ISME J, 2013(7), 1227-1236
One of the other podcasts I listen to is CBC Radios' Quirks and Quarks. I find it always interesting, and often profound.
The segment I was just blown away by was this one: http://www.cbc.ca/quirks/2014/03/15/2014-03-15-1/.
It put together many of the keywords I have heard from your podcasts, and added a new one- "host-defence peptides".
It even made me consider what are "biofilms", a term I have heard you use but never thought significant.
So. as something different, would you consider reviewing this radio segment as you do a paper? You could bring into the discussion regular papers that are relevant, too.
And, a final question, what ARE biofilms and what are their significance?
Thanks for doing what you do (even though I understand 25% of it).
Dear Dr. Racaniello,
In your latest TWIM (#72?), I heard you wonder out loud why a virus such as polio managed just fine without virulence whereas one such as norovirus seemed to relish it.
Might the answer have something to do with the work of Dr. Graham Rook at University College, London? His Old Friends hypothesis (a re-formulated hygiene hypothesis) distinguishes between microbes that inhabited hunter-gatherer hominids before we lived in cities (like hepatitis A and H/ pylori, which protect against allergies/asthma/autoimmune diseases) and those more recently evolved to infect humans living in sufficient population densities to support epidemics (like measles, which does NOT protect against a/a/a).
Maybe virulence evolved as an adaptation to crowds?
Just a thought,
P.S. My mother's family has the name Ianiello, which means--maybe 500 years ago or so--our families may have known each other. Just another thought.
I just got around to listening to episode 12 “Photothermal Nanoblades and Genome Engineering”. Your comment that it would need to be scaled up before it was practical for some of you to use intrigued me. I did a quick Google search and I didn’t see any recent articles addressing scaling up the process though I’m sure that there are groups working on it. In my own amateur fashion, I’d like to suggest an approach to such a process.
I believe that technology applying microfluidic flow cells to single cell streaming is reasonably well-developed currently and improving all the time. If you installed the insertion capillary tube into a microfluidic flow cell and added a photo-sensitive trigger to the capillary tube, then it should be fairly practical to mass insert bubbles of materials into cells fed through the flow cell and collected on the other side. Although flow cells would, most likely be tailored to particular cell sizes, it might be possible to make the insertion point slightly generic (i.e., slightly larger) by using laser forceps to automatically direct and immobilize the cells during insertion.
The main restriction would likely be finding a cell culture that would support the microbe in question with sufficiently low viscosity so as to flow through the cell with ease while prevented undesirable cellular effects (such as clumping or lysing) while the cells are waiting to inject. High cell density at the input reservoir could probably be achieved by centrifuging the initial culture then micro-diluting up the resulting pellet.
Although this may not prove to be the most efficient way to mass-process cells, I do see another potential advantage in using a microflow cell. With additional solvent input channels before and after the insertion point it might be possible to chemically manipulate the cell’s immediate environment for periods of milliseconds to seconds in such a way as to make them momentarily more amenable to insertion without long-term consequences to cell survival. Such manipulations would be easy to study, cell species by species in these flow cells until a manual of cells and optimum manipulation conditions could be generated.
Anyway, thanks again for the fascinating look at research that I don’t get a chance to look at very closely often (or understand).
25c in Palo Alto, California.
I think humans (us) are so enthralled by the idea and stories of symbiosis because we see it as unusual. Even though our world is full of symbionts, life relies on symbiosis, we are blind to it most of the time until extraordinary examples are pointed out to us. These make great examples of the "precision", depth and complexity of evolution and of life.
It's easiest to make a headline in our mind when we see "small" examples of tightly woven systems than to keep the whole ecosystem of metabolism in our minds.
Thanks as always for the amazing education and entrainment,
Tarwin - Developer / Designer
Just wanted to make a point about organelles vs symbionts.
You suggested that the difference might be that if all cells in the organism have it then it is an organelle; however not all plant cells have chloroplasts.
Might the difference be just how high up the taxonomic tree the symbiosis goes?
TWIM 74, about 26 minutes in.
the difference between enbosymbionts and organelles is:
1. WHEN it happened and
2. how much it increased fitness.
the endosymbioses that resulted in mitochondria and chloroplasts happened many billion years ago and apparently conferred selective advantage to recipients cells (future eukaryotes) over nonrecipients (future prokaryotes). we only have to wait a few billion years to see if the same is true for the endosymbionts discussed.
Dear Twim team,
Thank you for all the great episodes; I'm loving every single one of them!
I'm very pleased to hear more discussions on fungi-related subjects, being from Lithuania myself, I wait every year for the mushroom season, so that I could go and collect them. We even have national competitions for who can collect the largest number of mushrooms or find the biggest variety of them :)
On the mushroomy note, I would like to draw your attention on a recent paper describing the first fully sequenced genome of arbuscular mycorrhizal fungus, I think it's worth discussing.
"Genome of an arbuscular mycorrhizal fungus provides insight into the oldest plant symbiosis" http://www.pnas.org/content/110/50/20117.full .
The second paper that caught my eye, was describes how S. aureus "intentionally" induces pain through neurone stimulation, in order to suppress immune system's response to the infection. I think it very much makes one think about systemic control of the immune system and, as ever, the unexpected ways that bacteria have evolved to evade it.
"Bacteria activate sensory neurons that modulate pain and inflammation"http://www.nature.com/nature/journal/v501/n7465/full/nature12479.html
Hello TWiMsters! I recently discovered the trifecta that is the TWi series, and now I can’t get enough of your discussions of all things micro. For graduate students like myself, keeping up with the scientific literature can all too easily become just a means for cramming information into our brains that we feel we “should” know. Not only do your shows keep my mind stimulated and expose me to scientific papers that I might not otherwise read, but the informal and enthusiastic nature of the programs are just the slap in the face I need to crawl out from under the stack of papers, and remind me that I actually love to learn about science and to think about the various implications that a particular finding or result might have. After listening to your conversational discussion format and your fantastic insights that tie together the biology of the organism (or virus – are viruses organisms?) with the environment, host, experimental techniques etc., I am finding new clarity in the way that I think about scientific problems and evaluate scientific papers. I can’t commend you enough for what you do. Formal presentations of scientific findings are a dime a dozen - listening to world-class scientists “chat” amongst themselves about current topics in microbiology is an invaluable resource that few people really ever get a chance to do, until now. THANK YOU!
On a scientific note, I was recently listening to TWIM #43 and your discussion on the stable formation of caveolae in in E. coli. It was mentioned that it had previously been thought that stable caveolae formation in eukaryotic cells requires cholesterol, to which Michael replied that “there is [no cholesterol] in our friends the bacteria”. Although this was and is true in the context of E. coli and the paper’s findings, I think it is worth pointing out that there are several described examples of free cholesterol and cholesterol-containing glycolipids in bacterial outer membranes – namely in Helicobacter, Mycoplasma, Ehrlichia, Anaplasma, Brachyspira, and Borrelia species. In Borrelia burgdorferi, cholesterol containing compounds have been shown to form organized lipid rafts both in culture and in animal-derived organisms, with physical properties similar to that in eukaryotic membranes. A recent paper published in PLOS Pathogens in January of 2013 utilized fluorescent and radiolabeled cholesterol to demonstrate that B. burgdorferi extracts cholesterol from the plasma membrane of eukaryotic cells, and that prokaryotic cholesterol-glycolipids can be transferred to epithelial cell membranes through both a contact dependent mechanism (using direct attachment) and a contact independent method (through released outer membrane vesicles). I highly recommend looking in to this story (maybe as a TWIM topic?), as it provides a shift in the thinking about lipid rafts, expanding their biological relevance to prokaryotes, and could have implications for the evolution of the eukaryotic cell membrane structure. Additionally, transfer of antigenic lipids from bacteria to host cells could play a role in pathogenesis - having multiple consequences for the host immune response and potentially contributing to heightened inflammation, and perhaps even direct targeting of the cells themselves by immune effectors. I’ve provided the citations and Pubmed links to a few papers on the B. burgdorferi story below, but also recommend digging into the story for H. pylori.
I’ve rambled enough for now, I should run – I’ve got to get to iTunes to write a good review or two…
LaRocca TJ, Crowley JT, Cusack BJ, Pathak P, Benach J, et al. (2010) Cholesterol lipids of Borrelia burgdorferi form lipid rafts and are required for the bactericidal activity of a complement-independent antibody. Cell Host Microbe 8: 331–342.http://www.ncbi.nlm.nih.gov/pubmed/20951967/
Crowley JT, Toledo AM, LaRocca TJ, Coleman JL, London E, et al. (2013) Lipid Exchange between Borrelia burgdorferi and Host Cells. PLoS Pathog 9(1): e1003109. http://www.ncbi.nlm.nih.gov/pubmed/23326230
Department of Veterinary Microbiology and Pathology
Washington State University
“The truth is incontrovertible. Malice may attack it, ignorance may deride it, but in the end, there it is.”
- Winston Churchill
During TWiM#46 it was discussed that spores are able to sense peptidoglycan that has been shed by other bacteria. I would like to know, are the spores able to differentiate between the peptidoglycan that is shed by growing bacterial neighbours and the peptidoglycan lost during lysis.
University of Victoria, BC, Canada
Jon Dworkin answers:
Excellent question! If this any indication, your listeners are really paying attention!
Spores are able to differentiate between peptidoglycan fragments generated from growth and those generated by lysis since these processes in fact produce different PG fragments. Those resulting from lysis are thought to be produced largely by lytic transglycosylases which generate PG fragments containing an anhydro (non-reducing) end, whereas fragments produced in growth do not contain this group. In collaboration with Shariar Mobashey, an excellent PG chemist at Notre Dame, we demonstrated that synthetic muropeptides containing an anhydro group do not stimulate growth but synthetic muropeptides that lack this group are able to stimulate spore germination. Thus, spores can differentiate between cells in the milieu that are lysing versus those that are growing.
Finally, I can send an intelligent comment (re: TWiM #51) ...
Dear esteemed doctors,
I am sincere in this appellation as one of your many listeners who depend upon your unbiased fact finding and enlightening delivery to both educate and debunk with the latest information.
You have often remarked on the contradiction of the numerous pathogenic bacteria in common public areas while you as individuals do not feel endangered. In commenting on a letter read on TWIM 72 you mentioned the "cloud" of toilet-originating microbes created with every flush, yet a lack of evidence of resulting disease. It comes up also in regular mentions of door knobs, railings, phones and other public conveniences. Often this is attributed to the protection provided by a healthy immune system.
My question is whether the mechanism of microbial balance achieved in the human microbiome should be applied to understanding the forces at work in these external environments. Might our Linus-like microbial cloud function like the often mischaracterized schmutzdecke which purifies much of our drinking water?
Analyzing the potential health affects of environmental microbes apart from the greater human and environmental microbiomes seems a bit like analyzing the path of stars orbiting the earth. Am I wrong to assume that the microbial community of the toilet, room air, hands, nose and mouth have a significant impact on the danger from most of the individual microbes within those communities?
It's 252 degrees absolute, (or minus cold aught six on the Retrograde scale) this morning in sunny Connecticut.
A sincere thanks to you all for your dedication to TWIX. The world is listening to you more intently every day, and better for it.
Thank you for the great podcast! You've explained our story very well and it was funny to listen to it. I didn't know that "Speak friend and enter" is from lord of the rings! I just wanted to explain the name CYCLOPS because this was a question mark in the podcast. This is a link to Yano et al. 2008 where they describe the cyclops mutant phenotype in fig. 1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2629324/ In the WT the fluorescently labeled rhizobia enter the root by the formation of an infection thread. In the cyclops mutant, the root hair curls around the bacteria but further infection is impaired. And because this looks like an eye of an cyclops, the mutant derived its name from :-)
Hello all! I am a graduate student at UNC Chapel Hill in the Microbiology & Immunolgy department, and since my lab is mainly focused on the immunology section of that I try to supplement my microbial knowledge with information gleaned from other sources like your podcasts (Though I am a particular fan of parasites and TWiP). And as you can probably tell from this comment being so behind, I am never caught up with the podcasts, though I listen to them regardless.
You all mentioned that perhaps due to the high salt levels and temperature of the lake the haloarchaea from TWiM 68 act very similarly to when you perform a transformation in their extremely high gene transfer rate. Wouldn't it be fairly easy to test this theory since the authors demonstrated that they grow at many different temperatures? You could follow growth at room temperature and examine if comparable gene transfer takes place. I just wondered if any had considered looking into that to determine if that is the case. Thanks!
While your show has been a real eye-opener for me in so many ways, much of my interest in the microbial world remains in the areas of endo- and ectophytic microbes, soil microbial ecology, and food / energy / raw materials fermentation. You speak frequently (and, I have noticed, rather lovingly) of exploratory deep genome sequencing just to try to find out what’s in the environment. Though a little more narrowly focused, that is exactly the kind of research that I am reading about frequently in my areas of interest. What is the microbiome of a Withania leaf?, miso?, apong (wine / beer from moldy rice)?, hydrogen-bubbling mud?, and other topics of that nature.
I won’t pretend to understand all the techniques that are being used to genetically identify the microbes in these environments but it is of interest to note that much of what we thought we knew due to culture techniques isn’t particularly accurate. Culture techniques often skew results towards easily culturable microbes which can greatly distort our reconstruction of microbial communities (especially reconstructions of microbial succession) and completely misses the contributions of NCO’s (Non-Culturable Organisms). Recent techniques involving direct analysis of DNA present has greatly expanded out knowledge of these communities but different techniques often produce different results. We are still expanding and improving these techniques and, more importantly, learning how to apply them so that they complement each other’s strength and weaknesses and give us unprecedentedly clear views of microbial communities.
With all that introduction done, I now present my question. I assume that deep genomic diving involves many of the same techniques used in the shallower explorations mentioned above and viruses definitely provide a deep and wide pool of NCO’s. Would you be able to discuss some of the major DNA / RNA detection techniques used in this field in terms of their strengths and weaknesses and how different researchers are overlapping their use to build robustness into their studies of microbiome and virome?
Thanks for the great podcast,
First, thanks to Vincent et al for the wonderful podcast series (all 3). I am a fellow in pediatric infectious diseases (a fellow is the MD-equivalent of a post-doc for subspecialty training). Your podcasts are thought provoking and timely and always intellectually stimulating - so thank you.
In return, the temperature here in Cleveland Heights is currently 15oF, winds west at 7mph, humidity 72% and I'm really tired of winter.
Regarding TWiM #72: your discussion of this paper coincided with my caring for a patient with a surgical procedure known as a ureterosigmoidostomy, in which the ureters are implanted into the distal colon when the bladder is not present or can't be used for some reason (e.g. congenital malformation). In the process of caring for this person, I learned that there is a significantly increased risk of cancer developing in the bowel (see references below). After this surgery, the urine drains into the bowel and greatly changes the chemistry and flora present. Examination of the microbiota and/or metabolome of these patients may turn out to be quite interesting.
Thanks for making me think differently about our relationship to micro-organisms every day.
Alice Sato, MD PhD
1. Eur Urol. 2011 Nov;60(5):1081-6. doi: 10.1016/j.eururo.2011.07.006. Epub 2011 Jul
Tumor growth in urinary diversion: a multicenter analysis.
Kälble T, Hofmann I, Riedmiller H, Vergho D.
2. BJU Int. 2010 Mar;105(6):860-3. doi: 10.1111/j.1464-410X.2009.08811.x. Epub 2009
Long-term outcome of ureterosigmoidostomy: an analysis of patients with >10 years
Tollefson MK, Elliott DS, Zincke H, Frank I.
3. Acta Chir Belg. 2009 Jul-Aug;109(4):531-3.
Complications associated with ureterosigmoidostomy--colon carcinoma and ascendens
infection resulting in nephrectomy: a case report.
Turedi S, Incealtin O, Hos G.
4. J Urol. 1990 Sep;144(3):607-10.
Current status of tumor of the bowel following ureterosigmoidostomy: a review.
Husmann DA, Spence HM.
I was wondering if you all had seen this recent paper on detection of oral bacterial DNA in synovial fluid. Given that one of the frequent hosts teaches dentists I would be especially interested in his comments about the relationship of periodontal bacteria in other diseases. I think it’d make a very interesting discussion for non-microbiologists like myself. (My background is physics)
A doctor friend of mine created an rss feed on the topic so it seems like there’s been a lot of work done on this.
Hello Team TWiM,
I’ve followed with interest your coverage of Michael’s research into use of copper to fight hospital infection. Of all the interesting papers covered in 2013, I think the one most actionable is episode 55, The Copper Room. His research, described in that and prior shows, addresses an under-reported aspect of our health care system. Hospital acquired infections are a serious matter of which I am especially mindful as I prepare for surgery later this month. Kudos to Professor Michael Schmidt for proving how a relatively simple change of hospital materials can have a huge impact on improving patient health and outcomes.
Let me share some news, and ask follow-up questions.
Monday, 1/6/14, at the Consumer Electronics Show, Corning Inc introduced a new line of “Gorilla Glass” that it claims is the "World’s First Antimicrobial Cover Glass”. Links with information:
— press release: http://www.corning.com/CMS/Overview.aspx?id=60899
— video releases: http://www.youtube.com/watch?v=egU8GLD7MG8&feature=youtu.be
Corning is positioning the product for touch-based mobile devices to combat bacteriological growth and spread of disease. We have all have seen phones whose surfaces are, in plain speech, gross, disgusting and covered with layers of schmutz. TWiM listeners would call such objects “fomites” to use a polite, abstracted, and neutral term.
Here come my questions ….
1. Corning highlights the use of “ionic silver” as the antimicrobial agent in its new glass. Silver, Ag, is in the same column and one row below copper, Cu, in the Periodic Table. Below silver is gold, Au. Do I recall my chemistry correctly in that each has the same number of valence electrons? If this is true, can Michael or other hosts compare-and-contrast how Cu/Ag/Au vary in effectivity killing bacteria? Besides economics, is any of those metals a preferred choice for bacterial killing agent? Why, or why not? Is the preference related to their increasing conductiveness as you descend rows in the Periodic Table?
This question is truly cutting edge… I call your attention to
2. Would you describe in more detail the mechanism by which copper’s valence electrons kills bacteria?
3. What impact does copper have on neutralizing viruses and their ability to spread? I use “neutralizing” because you can’t kill a non-living virus. Do you agree with this phrasing?
Wishing all of you the best in 2014.
PS - the weather. Here in the San Francisco Bay Area the weather these past few days was mostly sunny, with highs in the mid-60’s and lows in the mid-40’s. This east coast refugee empathizes with easterners like TWiM’s Michiganders, Carolinians, Jerseyites, or his brother out on Long Island who have been experiencing extreme cold with daily highs in the low-teens. Only Elio’s San Diego has better weather as I write this.
Greetings Vincent and Team,
On the foremost, thank you for your excellent educast. Your podcasts has helped me generate and understand a lot of ideas which i would have never accomplished had it not been for your podcast. I have just joined, Dept of Neuro-Microbiology, NIMHANS, Bangalore, India as a PhD scholar. Maybe i can consider it a TWiX bump.
The issue of Health Care associated infection has come up, multiple times in your podcast. I have a query in connection with the same.
Hospital environment harbors microbes usually of MDR type. The ones commonly involved in Nosocomial infections are often environment and antibiotic resistant types. There is a very limited scope of competition from harmless and less robust environmental flora. I'm curious if we could (theoretically at least) introduce environmental flora into hospital regularly, which would then reduce hospital acquired infections. Just a wandering thought.
I always have wondered why doesn’t TWiM have Pick of the week. Keep up your excellent work. Never ever stop TWiX.
A yet another TWiX Podcast fan.
Hi Vincent, Elio, Michael and friends,
Firstly, thanks for the show. It regularly blows my mind, and keeps me very engaged during the otherwise cold and rainy walks into work. Keeping up with each episode has very much broadened my mind to microbiological topics that I wouldn’t have come across otherwise, which has in turn enriched my own thinking and work.
In the fascinating TWiM 68 ‘The Fungus Among Us,’ Elio questioned the existence of uninhabited aqueous environments. I know of two naturally occurring habitats on the earth that are most probably functionally sterile (that is, supporting no active growth). These are Discovery Basin in the deep Mediterranean and Don Juan Pond in the McMurdo Dry Valleys, Antarctica. Both of these are extremely concentrated brines, where the main salt is not NaCl, but MgCl2 (in the case of Discovery Basin) and CaCl2 (in Don Juan). Previous studies report DNA sequences from Discovery basin, but the current thought is that these originate from organisms that live above the seawater/brine interface and have simply sunk into it. mRNA has not been successfully recovered, suggesting that there is no active life. Exactly what property of the brine precludes life is not fully understood; it could be either the dramatically low water activity (availability of free water) or the chaotropic, disruptive effect MgCl2 has on biological macromolecules. Check out this paper which discusses support for a chaotropic barrier to life:
Don Juan is a particularly fascinating place, as it never freezes over despite experiencing temperatures down to -40oC. There is much less published biological data on this environment (none with molecular tools), but it is more chaotropic and more concentrated than Discovery brine, and most microbiologists who work with Dry Valleys lakes consider it a sterile environment. These environments are particularly interesting because of the current paradigm (in astrobiology) of liquid water being the holy grail for habitability, and yet even on the earth there are (albeit rare) examples of aqueous environments that may fundamentally preclude life.
On a different note, I thought you might all enjoy this paper exploring some of the novelties of haloarchaeal genome replication:http://www.nature.com/nature/journal/v503/n7477/abs/nature12650.html
I was reminded of it by your discussion of horizontal gene transfer in the archaea. It’s a really nice study and highlights how different and interesting these organisms are when compared to bacteria or eukaryotes. The authors hint toward some profound evolutionary implications in the discussion.
Apologies for the ramblings, and thanks again for all the inspiring discussions.
UK Centre for Astrobiology
School of Physics and Astronomy
The University of Edinburgh
If you can find the backstory to this, it would be an interesting TWiM:
"Passenger with possible TB infection pulled from plane"
A friend of mine just posted this question on tumblr and I thought you all would be the perfect people to address it:
Question of the day: A strain of Flavobacterium (KI72) evolved the capacity to digest nylon, obviously in recent history. Fine and well. How long will it be until one of the cariogenic bacteria species evolves the ability to digest dental resin? After all, we are putting a lot of it on their dinner table.
Original Article: http://recursivemuffin.tumblr.com/post/68921313389
Hi, great podcast. I just wanted to let you all know that stool taking "the shape of the container" isn't a British-ism. I work in the Micro department of a hospital/reference lab and we use this criteria on a daily basis when testing for C Diff. Specimens that are too formed must be rejected for testing, and we've had many discussions about what makes a stool formed or not; the criteria "takes the shape of the container" has turned out to be the best way to decide if we will reject a specimen or not.
Dear Magiis of the Microbes,
In the news here in Sweden there are unfortunately many reports about the spread of C Difficile, and we've had a few deaths as well. Remembering Michaels research about copper surfacing as a means to reduce harmful microbes in hospital settings, it may be of interest to learn that a study has been conducted here to show that using Chlorine and a detailed cleaning protocol reduced infections by 50%. I have not found the publication, but here is (in Swedish) the protocol recommended: http://www.lj.se/infopage.jsf?childId=16504&nodeId=31555. Essentially they swipe all surfaces with Chlorine.
Here is another article about the research in a Swedish medical Journal: http://www.lakartidningen.se/Klinik-och-vetenskap/Vardutveckling/2014/01/Lomskt-och-omfattande-utbrott-av-Clostridium-difficile/
I do not want to make the impression it was unknown that chlorine is effective as an antibacterial. CDC knew this (http://www.cdc.gov/hicpac/disinfection_sterilization/3_2contaminateddevices.html)
Thank you all for a very interesting pod cast!
My name is Jim from Vancouver. I have no formal education in phraseology but am an enthusiastic follower of TWIP, TWIM & TWIV.
Recently I followed a program about yeast infections and the threat to public health they can pose.
My question is would it be possible to isolate the infectious yeast agents and brew a beer that would act as a vaccine against these infections. I understand that the brewing process kills the yeast so there would be no chance of contamination by the dead yeast which would be filtered out in any case. There were plans at one point to add vitamins to beer at one time to improve public health so the idea is not that unusual.
The question is Would this brew provide a heads up to the immune system that would prevent yeast infections from taking hold?
Also, would it be possible to have a TWIF - This Week in Fungus podcast as part of your audio library? There are so many other valid topics that fungus tends to be neglected.
Vince and Dickson, keep up the good work.
I was catching up on the podcasts and in TWIM 64 you discussed antibiotic resistance and connections between animals husbandry use and human disease issues. A recent article in Science “Distinguishable Epidemics of Multidrug-Resistant Salmonella Typhimurium DT104 in Different Hosts” <http://www.sciencemag.org/content/341/6153/1514.full > seems to indicate a lack of transmission from animal to human populations.
A comment was then made that the same potential transmission problems would be true for aquaculture animals, where antibiotic resistance is also an issue. However, we need to keep in mind that there are very few pathogens for fish that are zoonotic (excluding helminthes that go between bears and wild salmon and seals and some fish) and most aquatic pathogens don’t grow at human body temperatures. Even more important, antibiotics almost triple the cost of fish feed and very few antibiotics are allowed and those are only for a few species. Unlike pigs and chickens, where adding antibiotics to the feed improves the growth rate and decreases feed consumption, adding antibiotic to fish feeds provides no growth effect and actually decreases the animals immune system (Rijkers, Teunissen et al. 1980) – not good for husbandry.
I had previously sent to TWIV the following graph showing that decrease in antibiotic use in Norway salmon production as vaccination solved the problems.
Notes: Use of antibiotics (yellow line) and amount of fish produced (blue columns). The numbers on the leftside are the tonnes of fish; the numbers on the right side are the tonnes of antibiotics.
Sources: NMD & Directorate for fisheries, as cited in Ministry of Fisheries (2002).
Activist organizations, including PEW, have had a multi million dollar “de-marketing” campaign against aquaculture in the US and have succeeded in framing the images in the society.
Other aquaculture myths that are sold to the public by environmental activists are caused by the mandated “color added” label on farmed salmon when you include astaxanthin in the diet, despite the fact that the chemical is identical to the astaxanthin that makes wild salmon pink. In addition, most people in the US believe that salmon and other carnivorous fish require fish meal in their diets and are thus depleting the ocean resources. We know enough about fish nutrition to create totally “vegan” diets for carnivorous marine fish which out-perform fish meal based control diets. However, the ingredients used in these vegan diets are also useful in chicken, and pig diets and fish meal is less desirable for these species (it makes chicken taste like fish and egg yokes grey). Economics pushes fish meal into fish diets, not biology and this whole fish meal issue is manufactured by activists for emotional appeal. If all aquaculture went away, the fish meal market would shift back to pigs, cows, chickens, dogs and cat feeds, just it was before aquaculture was a significant business. The international harvesting of fish meal has been constant for about 4 decades while aquaculture has grown by a factor of about 100 times.
One of my interest in listening to TWIV, TWIM, etc. is related to the observation that aquaculture systems are really controlled by the microbiological ecologies. It is like the complexity of the human gut interactions extended to all inside and outside surfaces. This makes discussions on TWIV about phages sticking their heads in mucus very fascinating to me. This effectively put the phage between its bacterial host and the host’s dinner on the animals surface. A very good location for an ambush hunter phage that has almost no mobility (Brownian motion).
I could go on about how aquaculture can solve the food (meat) problem for the coming 3 billion more people on this planet (better meat yield, better food conversion efficiency, when the animals doesn’t have to stand up or keep warm). The world wide growth rate of aquaculture (doubling in about 8 years) will mean that the talents of the TWIV, TWIM scientists will be required to understand how these microbiological ecologies really work and how to control the outcomes. We are seeing research dramatically increasing in every area relevant to trying to understand and control the microbiological ecologies of these complex systems ranging from probiotics, prebiotics, to specific phages for specific bacterial problems (aquatic phage therapy), but the sources of this research are primarily outside the US. As aquaculture takes over the meat production business with its higher conversion efficiencies, the need for scientists who understand these complex systems will increase. Many of the TWIM TWIV followers will have a bright future opportunity outside of conventional academic research.
Sorry about being a bit long winded. Love your programs.
Dallas E. Weaver, Ph.D.
Acellular pertussis vaccine
Thanks for the amazing stuff. Shows how much we have yet to learn.
Cough is an endobronchial symptom. Even whooping cough can be temporarily ameliorated by anaesthetising the epithelium by the inhalation of nebulised lidocaine, the technique used prior to bronchoscopy.
My medical school microbiology is almost from the era of hunter-gatherers with their sticks and stones circa 1968.
If the volume of human knowledge is a sphere, the area of our ignorance (the "known unknowns" - h/t Donald Rumsfeld) is the surface of the sphere. The volume increases by the cube of the radius while the area increases by its square. It leads to the correct perception that our area of ignorance is decreasing relative to the volume of our knowledge. However what lies beyond the surface of the sphere (the "unknown unknowns") is beyond our ken: just as Flatlanders cannot grok what's beyond the dimensions of their world, we cannot grok those unknown unknowns.
"Expelling fomites" - Dr. Michael Schmidt
Fomites are objects (usually solid) in the environment which may (usually passively) harbour microorganisms.
The germ enlarger. Breakthrough in microbiology, which I am surprised is not used today or discussed on TWIM.