mailboxTWiM 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 67 Letters

Jim writes:


The last 10 minutes or so of the Mike Tech Show podcast 447 covers Mike's music collection of some 30K tracks and he may have everything Frank ever did. He is linked to the Apple music system and your daughter might be able see what he has, etc. Just a thought. Plus he discusses some useful apps she/you might use, if not already using them.

Smithfield, VA

Jim writes:

This link from quora asked the question in the subject and includes many comments I found interesting. Your listeners might be interested?

Smithfield, VA

Kehaulani writes:

Aloha TWIMsters;
I must start by saying that I love your podcasts and have been listening since TWIV day 1 (really) and thank you so much for providing such and informative and entertaining discussion on the issues related to microbes. I just saw this article, A Case Study of Gut Fermentation Syndrome (Auto-Brewery) with Saccharomyces cerevisiae as the Causative Organism, referred to in the news and had to send it to you for comment. The authors conclude with a message to health care workers that treat patients for alcohol intoxication that claim to not have been drinking and how this condition can have serious social costs if misdiagnosed. I wonder if this condition is more prevalent than we realize due to the increase in a diets high in sugar and carbohydrates as well as the use of antibiotics that disrupt the gut biome, which allows the overgrowth of this commensal yeast. I guess it gives new meaning to being addicted to carbs :)

B. Cordell and J. McCarthy, "A Case Study of Gut Fermentation Syndrome (Auto-Brewery) with Saccharomyces cerevisiae as the Causative Organism," International Journal of Clinical Medicine, Vol. 4 No. 7, 2013, pp. 309-312. doi: 10.4236/ijcm.2013.47054.

Ralf writes:

Hello TWIM,
the brain microbiome paper you discussed seems to have been largely ignored by the press. However, Mark Pallen sent you an open reply where he was dismissive of the claims of the paper, comparing it to elusive XMRV and arsenic life. He also says effectively the authors didn't do their homework.

If you can't find his letter in your mail here is the link:

I am writing because I strongly disagree with Pallen's opinion and would like to see your opinon on Pallen's letter. Indeed, I think the authors went to great lengths to get the result using different methods. And they have cultured the critters, read the part where they inoculated the mice with heated and non-heated brain tissue.The only way this could not quite be what it seems is that the bacteria are not in full bloom but dormant, like M. tuberculosis sleeping in macrophages. Low transcriptional activity they have found actually supports this hypothesis.

I'm a former biocurator who only did a bit of library work on M. tuberculosis, so that paper rang a bell with me.

Many thanks for your work and for bringing up that paper which probably has sparked some frantic activity by now I'd guess...

Regards, (and check the citation below)
Ce sont les microbes, qui auront le dernier mot. (Pasteur)

Tim writes:

Dear Vincent & Michael,

In TWIM 64 the episode on URI & UTI you and the guests get on the subject of agriculture and antibiotic resistance in microbes around 56 minutes into the video. Michael mentioned that manure is suppose to be heated before application to fields and indicated its not and if was it wouldn't be sufficient to destroy DNA which I'm assuming he meant plasmids containing resistance genes. I know it wasn't the focus of the show and time didn't need to be devoted to fully discussing the roles of animal agriculture and manure in microbial resistance but I feel there may be some clarification needed. Manure lagoons were discussed in which case we are talking liquid manure and not something you'd apply to land growing crops for human consumption. I'm sure it's legal in the case of a sufficient waiting period from application to planting although I'm not very versed in the exact specifications as I'm a dairy farmer not a vegetable grower. By heating I think Michael was referring to composting of manure. This is a process that in the case of organic farming and I'd assume conventional as well is supposed to be carried out with strict controls involving temperature measurements and records along with scheduled aeration and the like to make a product allowed for use in human consumption crops. There is a lot of interesting research out there on prevalence of antibiotic resistant genes on farms, in manure, in soils on farms, and comparisons of different operations. This could be a possible future episode for you in an area you usually only dabble in on occasion, that being agriculture. Here are some links to papers I could find on the subject I've found interesting:

I could go on for hours about this subject and its implications for agriculture and society as a whole but I need to get to the farm milking. Have a great day.

Tim Zweber
Zweber Farms

Kehaulani writes:

Aloha TWIMsters,

Just wanted to thank you for all the work you do bringing the world of microbes to the masses ;)

As a student in Microbiology, I listen to all the TWIx podcasts and enjoy them all :) Last year, I wrote a paper on the gut microbiome and came across a paper that might identify a causal agent in obesity (citation below). I am not sure why it did not get the attention (both media and scientific) that the paper you discussed this week since it seemed to be similar in focus. It seems that inflammation plays an important part in obesity and the presence of the bacterial toxin might be the culprit. The researchers concluded that endotoxin-induced inflammation might have a pivotal role in obesity (as induced by the bacteria E. cloacae strain B29). The man in this study lost weight when switched to a whole grain diet with probiotics and the bacterial strain was undetected. I wonder if the paper you presented obtained a similar result in mice fed a low fat diet where the gut microbiome contained a healthy diversity. There have been many studies that show a diet high in fat and sugar contributes to obesity, but could it also maintain an unhealthy gut microbe that could produce an endotoxin that stimulates inflammation? In the study you mentioned that the diet was important in maintaining a healthy gut diversity. I guess this means that the use of any prebiotic for weight loss would be meaningless if not accompanied by a low fat diet? How does this explain those that are thin and eat an unhealthy / fast food diet? I know this is a complex issue but I can't help but think of the effect of an endotoxin producer and resulting inflammation as a likely culprit in obesity. I feel for those that have been frustrated by the "calories in = calories out" statement .. these studies show that it is not that simple.


Na Fei, Liping Zhao, 2013. An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice. ISME J. 2013 April; 7(4): 880–884. Published online 2012 December 13. doi: 10.1038/ismej.2012.153


TWiM 66 Letters

Neva writes:
You may have seen this. Thought you all might enjoy this header illustration from

All your podcast are my favorites!

Dan writes:
Hi guys,

(I should give the obligatory "love the show", but it is true: as a bioinformaticist of a fairly mathematical sort, it's nice to spend an hour a week really listening to why people care about comparing metagenomic samples, say, rather than just thinking about them as mathematical objects to be manipulated and analyzed.)

Anyhow, there was a question on TWiM about whether people wearing their scrubs home spread infections from hospitals to other environments. Vincent says people in NYC rarely wear scrubs on the subway there. Regrettably, that's not true here in Ontario. The bus I was riding while I was listening to TWiM stopped in front of our local hospital...and on came a woman wearing scrubs. And sandals!

Keep up the good work,

(here is the image)

Steve writes:

Hi Vincent,

Always amused by the repartee on your podcasts, especially towards the end; and today I particularly enjoyed the continuation of your banter over washing. It reminded me of a visit to my local hospital - a large one, serving a fairly sizeable conurbation. I had to go for an ultrasound, which was based in a far corner of the building on an upper floor. I walked all through the building, past many signs about washing hands and the need for cleanliness, and then sat down in a waiting room. As I sat there, I soon became aware of a nasty smell, and was dismayed to find I had picked up a sizeable unwanted faecal donation from what must have been a very relieved dog. With this contribution, I had left a trail of filth all through the hospital, and, if I were to get up on a gurney, I would transfer it to that - and possibly some of the staff - too. What was I to do?

As nonchalantly as possible, I removed my sandal, and found its treads firmly plugged with very sticky and smelly mess; so I went in search of a wash basin. There one was; with shiny taps (faucets), and modern scalloped basin. There were elbow levers on the taps, and a large notice on how to wash your hands... The thing was actually a safety design nightmare. The scalloped basin was shallow, and would slosh, and splash the surroundings. The tap outlets were low down on the basin and close to the sides, so you could not put anything - like my shoe - under them; anyone washing their hands would likely touch the sides of the basin. What should have been there was a deep, square sectioned, basin, with a high outlet mixer tap, delivering a good volume of water into the middle, such that hands, fore-arms, and any objects that happened to need cleaning, could be cleansed with a minimum of splashing. But, it was much worse than that. In their wisdom, no doubt, someone had decided that the public could not be trusted with plugs: but they had also decided they still wanted plugs. So they made a plug that was captive to the outlet grille; a plug that one could not take out, but which would fall in when the tap was turned on. Thus it was impossible to run something like a turd-befouled sandal under a stream of appropriately hot water, to save a hospital from the infections it carried. But my shoe *had* to be cleaned! So you can picture the scene: trying to get some water from a badly positioned tap, onto a mucky shoe, while endeavouring to keep a plug from blocking the tiny basin, without getting filth on one's self, or the surroundings! In the end there was only one way. I had to fill the basin, put the sandal in it, and scrub at it with paper towels. Then I had to put my hand in the filthy water, to hold the plug out while the water drained! Then I had to try to wash the basin; then my hands; then my hands; then my hands... Every time you wash your hands in this hospital, you either leave a basin full of dirty water for the next unfortunate, or you dirty your hands again to let the water out!

With thousands of people traipsing in and out of hospitals, without removing their shoes, - and without putting on masks, and hair covers - there isn't a hope in Hell of keeping out the germs. Without really well designed washing and toiletry facilities for both staff *and* public, there isn't a hope in Hell, of beating hospital acquired infections.

Love the show,

Best wishes,

Steve Hawkins
(Rather humid and sticky, after a hot sunny day.)

Chris writes:

Just before listening to the last TWiM I had finished reading <i>The Drunken Botanist</i> by Amy Stewart. It is like a garden tour of the liquor store, with history, garden tips, recipes and odd little bits of trivia.

On page 59 is a box titled "Warning: Do not add water." It then explains that during prohibition California grape growers sold bricks of compressed dehydrated grapes, with a package of wine making yeast. The label warned to not add water and the yeast, because it would lead to fermentation and that would not be legal. ;-)

This is the book's website:

Now I am going to try to make home made homemade grenadine from page 338 from a couple of pomegranates I bought this morning.

Thanks for the entertaining listening.


TWiM 65 Letters

Alexandra writes:

Dear TWIM-ers,

When I began listening to TWIV almost a year ago, I had just switched majors from philosophy to biology. I am now writing to you good people at TWIM at the end of my first undergraduate summer research gig, where I have had quite a bit of fun (and frustration) mucking about with wetland bacteria. As I've been reading about all these different Bacilli, though, I've been wondering about species identification among bacteria, and about what it even means to classify bacteria as belonging to different species.

As far as I understand, most of the current work on species identification and the evolutionary history of bacteria relies on comparing the genomes of bacteria, looking for differences and similarities in highly conserved regions and in the presence or absence of accessory genes. My adviser told me that one shorthand for distinguishing between a "strain" and a species is whether or not the genomes of the two bacteria are more than 95% related to one another. This seems like a fairly arbitrary figure to me!

Then, too, some species are very closely related but lead significantly different lives, in different environments. I have had the pleasure of getting to know Bacillus mycoides this summer, but I don't think I would have been able to handle this little bug if it behaved much like its more famous and dangerous relative, Bacillus anthracis. It seems to me that any species classification must take "lifestyle" - metabolism, behavior, environment - into account.

So how do all of you microbiologists think about this notion of "species" - how do you distinguish between a genus, a species, and a strain? Is it primarily down to differences in the genome, or do you care mostly about those differences which lead to substantially different ways of living?

Thanks so much for reading!

Your faithful listener,


Peter writes:

Dear TWiM team I thought that this was worth a mention.

The fungus Chalara fraxinea causes Ash Dieback disease and is killing many ash trees in Britain and Europe, losses in Denmark are believed to be 60% to 90% of all ash trees.

Dr Dan MacLean, of the John Innes Centre in Norwich came up with the idea of crowd-sourcing the analysis of the fungal genome and the genomes of susceptible and resistant trees through a facebook game:

The hope is that the detailed analysis will give clues to the origins of the disease, and help identify fungus resistant ash trees to grow in the future.
Top gamers may have their names published in scientific articles for their role in helping analyse the genetic information. Results of the project will be made available on the crowd-sourcing website OpenAshDieBack.

More on Ash Dieback:

Andres writes:

Hi TWIM Team,
I love listening to all your shows TWIV, TWIP and TWIM on Stitcher Radio. Thank you very much for the many hours of entertainment and learning.

On TWIM #61 it was mentioned that the body needs gut bacteria to make vitamin K and B. If you have not had a show on these bacteria I would like to suggest that these would make a good show topic.

Keep up the great work!

Thank you,
Fremont, CA

John writes:

Dear TWIMmers,

In TWIM #61, you talked about a species of insect with a symbiotic bacteria (which itself had a symbiont), and which also had a lot of bacterial genes that had been taken up into the insect's DNA. My understanding was that bacterial DNA and eukaryotic DNA have some differences that make it hard to move between the two. Do those differences cause a problem for movement of genes between insects and bacteria? If so, is there any indication of what has to happen for the gene transfer to work, and how common that is?

At the risk of slipping into TWIV territory, it seems like these endosymbionts would provide a lot of opportunity for infection of the host cell with bacteriophage. Are there examples of phage infecting eukaryotic cells?

Thanks for answering my amateur questions, and for your wonderful podcasts.


David writes:

In TWiM 60 during the email segment, there was a discussion about preservation of DNA in amber. Irregardless of Michael Crichton's book Jurassic Park, written in 1990, DNA preserved in amber has not panned out. Amber, which preserves in great detail the outer structure of insects, rarely preserves any internal material. Essentially, organisms in amber are casts. In addition, amber is porous to air, and air is corrosive to DNA. Searches for DNA in amber have not found much. Early 90's claims of DNA found in amber have been disputed. Vincent may recall my email answered on TWiV episode (I don't remember which one) about viruses trapped in amber. The article was behind a paywall so I was not able to read it, but I'm pretty sure no DNA was recovered.

FYI, DNA from bone has had more success. A recent announcement was made that DNA was recovered from a 700,000 year old frozen horse bone. So ancient DNA recovery is still possible, just not from amber.

See this You tube video by a paleontologist discussing DNA from amber.

Christyne writes:

Dear Vincent and fellow TWiMmers,

I really love your podcast. My son told me about them, and I have worked my way through the shows. I have been learning SO much.

I recently read that children with folic acid deficiency may have a higher incidence of regressive autism, and it got me wondering about the microbiome and nutrition. I heard Michael and maybe Jo? mention that the microbiome supplies 5-10% of your calories, and I found review articles that include references for that, but I haven't found a good review of micronutrients the microbiome supplies, like the b-vitamins. Would you consider having a TWiM on the microbiome and the nutrition it supplies? Since children with autism often have problematic microbiomes, could it be that they aren't getting the right vitamins at the right times for their brain development? Can the body "ask" the microbiome for more vitamins when it needs them through signaling? Could the microbiome supply much larger amounts of vitamins than we realize? Perhaps there are micronutrients that we don't know of yet because our microbiota supply them instead of our food?

I am interested in the vitamins because of my own story. (You could leave this part out if you want to). I used to be a bioengineer working in microscopy, gene arrays and bioinformatics, but I suddenly got sick with a disabling mitochondrial disease in my mid forties. I could run a mile without thinking about it, then a year later I couldn't sit up for 30 minutes, then a year after that I was going into heart failure. I started taking very large amounts of riboflavin and my heart, which had become enlarged, shrunk back to normal size and started working just fine! Unfortunately my other muscles didn't respond so well, but I'm still alive 5 years later, which wouldn't be the case without the riboflavin. Some of my friends on my mito and FOD (fatty acid oxidation disorder) support groups are also helped a lot by particular vitamins, and it makes me wonder why did it change? I was doing fine for 45 years then suddenly I need a bunch of riboflavin to survive. I'm starting to suspect the microbiome. I like how you think about it as another organ.
Thanks for your great work! Chris

There were various review articles in pubmed related to the microbiome harvesting energy and obesity and diabetes

The folate deficiency in children/autism papers are sort of patchwork, but here is a sampling

p.s. I love Elio's voice

(p.s.s. my genetic defects are normally mild ones in nuclear genes affecting fatty acid oxidation and complex 1 of the respiratory chain, so the odd inheritance and aging effects on mitochondrial dna disorders don't really apply to me)

Joe writes:

Dear TWiM folk,

Hi from Denver and ICAAC.

I'm delighted that you are finally devoting the time and attention to the most important microbiology of all--yeast fermentations.

Your letter last week from Mark on yeast inoculations reflects a very modern North American perspective on winemaking. Inoculations with clonal yeast strains are of course quite modern--wine was made for millenia without inoculation.

Many of the finest wines of France, Vincent, are fermented with their indigenous yeasts. A complex microbiome produces a more complex metabolome, unsurprisingly, giving wines of distinct complexity and subtlety of flavor. One man's complexity may of course be another's excess funk in some cases, taste is always paramount.

It is also true that choices in the vineyard may influence the success of native ferments--heavy spraying with fungicides, for instance, surely selects yeast populations. But so does weather during the harvest, tying the wine more closely to its vintage. The requirement of highly alcohol-tolerant yeast to finish the fermentations of high-sugar grapes reflects some climate change, but it also reflects a recent cultural preference in California for riper (and to my taste simpler) fruit flavors that come with grapes left on the vine later in the summer to eliminate "green" flavors and coincidentally raise sugar contents.

I hope I have the chance to wave from the audience at a live TWiM or TWiV this week, and I hope you will continue to give alcoholic fermentation the attention they surely deserve.



TWiM 64 Letters

Tim writes:

Vincent and friends,

While driving around a field cutting hay lost in my science podcast playlist the episode of TWIM #61 came up and I had to listen intently as salmonella typhimurium came up as this is a common enteric issue in agriculture. When you mentioned the work around salmonella came up with to outwit lipocalin and the idea people could in many millennia possibly evolve a second antisiderophore to combat it a thought occurred to me. Is modern medicine slowing our rate of evolution by reducing selection pressure for more fit individuals? This is not an argument for withholding medical treatments to improve the human race or something silly like that b/c obviously everyone has more important skills than the ability to fight off an enteric disease but was an interesting thought that hadn't really occurred to me before. Just wondering what you all thought of this.

Also thanks for the TWIP mention of our farm. I'll let you know if there's a TWIP bump like there is for TWIV ; )

If you decide to do an agriculture themed podcast like you and Dickson mentioned I'll be sure to listen to every episode as your opinions on agriculture are always well thought out and enjoyable to hear b/c it's interesting to see the views of very intelligent people that aren't directly in the field. Have a great day I need to get back to putting this hay down while the suns shining.

Tim Zweber
Zweber Farms

Sent from mobile device w/ a small keypad, forgive brevity and typos ; )

Click to listen to this episode of TWiM (64) Live in Denver from ICAAC 2013.

TWiM 63 Letters

Hugh writes:

Hi Vincent,

I really enjoyed hearing about Carl Woese in TWiM #50. You mentioned the controversy surrounding of Woese's 1977 discovery of Archea as a third domain of life, as it contradicted entrenched scientific beliefs. Although Archea soon found its way into general scientific thinking, his work brings up another fundamental idea that is still controversial today. It relates to the word 'prokaryote.' Norm Pace, one of Woese's former students, is a strong believer that we need to stop using this word. I think he makes extremely compelling arguments about the harm this word does to basic biological understanding, and thought this could be an interesting discussion point on TWiM. Here are the the titles of two papers by Norm Pace that discuss this issue. They're both geared towards a general audience: Problems with "procaryote" (Journal of Bacteriology, 2009); Time for a Change (Nature, 2006).

I recently discovered TWiM and TWiV and am now an avid listener, mostly while cooking dinner and washing dishes, which always seems like deja vu after a long day of experiments and washing glasswear at the lab. Thank you for making that process infinitely more enjoyable. Writing from Seattle, WA,


[we had a brief discussion of this on an early TWiM; Elio if I recall does not mind the term]

Megan writes:

Hi TWIM team,

Could you do a TWIM about the archea and viruses that infect them? It is a fascinating area that doesn't get as much attention as bacteria.



Jim writes:

Just another update on the hand-washing issue. This link discusses the article, which costs $10 to see at the journal.


Smithfield, VA

Mark writes:

Hello Vincent, Michael, Elio --

I enjoy TWiM, and have listened since episode #1. Keep up the good work and keep going. Out of TWiV, TWiP, and TWiM, I discuss episodes of TWiM with my wife the most!

I am writing, belatedly, to correct some inaccuracies in episode 49 "Grape-like Clusters". These are:

1. Someone, VR?, commented that French wines were the best. This is not FACT, but a matter of taste. The Latin expression "De gustibus non est disputandum" applies.

2. Michael speculated that natural yeast was used to ferment wine. This is a common belief and is mostly wrong. There is a vigorous industry dedicated to selling commercial yeasts to winemakers. A small number of boutique wineries are experimenting with using natural yeast -- these are a minority, and the quality of their results is highly variable.

I am an amateur wine maker of 17 years. See the attached image of a macro bin containing 0.5 ton of Cabernet Franc grapes from 2012. Note the white, powder-like color on the grapes -- this is natural yeast that grows in the vineyard. Note also the stems with missing grapes -- as harvest occurs the growers typically take weekly samples to measure sugar content.

In wine making, after the crush (in which a machine separate the stems from the grape berries, and in which the berries are lightly crushed) potassium metabisulfite is added to the must (the residual grapes & juice) to kill natural yeasts and inhibit fermentation. Typically 24 hours later the must is inoculated with a yeast starter and nutrients. The image of nubile virgins stamping barefoot on grapes to make wine is, sadly, a myth.

Our winemaking group purchases yeast from a company which supplies commercial wineries, Gusmer Enterprises. Attached is their 2012 catalog. Its front and back covers commemorate scientists whose discoveries were key to wine making -- Pasteur, Leeuwenhoek, Riley, or Dewar.

There are subterranean links to virology. Vincent can speak to physicist-turned-virologist Max Delbruck and his seminal work. Did you know that his uncle, also named Max --ück_(chemist) -- developed a yeast, Torulaspora delbrueckii, that will live in high alcohol levels? These yeasts are especially important in California because our climate products grapes with very high sugar levels which, through fermentation, produces high alcohol levels.

3. The paper that Michael presented provided a quantitative framework to characterize and measure the differences between grapes grown in different blocks on the research vineyard. As winemakers we see a qualitative difference in each barrel of wine. Rule of thumb: half a ton of grapes = 1 barrel = 24-25 cases of wine. It is too labor intensive to produce and label at such levels, thus wine from each barrel is blended which averages out the different tastes of each barrel.

I have TWO recommendations for listener-picks-of-the-week:

-- to learn about how a Californian coup d'etat established their wines as equals to French wine makers, watch the movie "Bottle Shock" which combines fact and Hollywood sensuality; watch the trailer here:

-- to read more about the entire process of making wines from growing grapes, figuring out when to harvest them, and fermentation I recommend the book "From Vines to Wines"

In closing,

in vino veritas


PS - feel free to use the grape image. The catalog image is technically copyrighted, though I doubt Gusmer would care if you want post it.



TWiM 62 Letters

Robert writes:
In TWIM #60 @1:06:23 Michael Schmidt suggests that glucose for fermentation from biomass is a necessary step in production of fuel ethanol. Fuel ethanol and other low molecular weight compounds can also be produced by autotrophic anaerobic fermentation of syngas. Syngas is a mixture of carbon monoxide, carbon dioxide, and hydrogen produced by pyroclastic treatment of a wide variety of organic material including ligno-cellulose, recycled tires, sewage sludge, and natural gas or methane. These reactions have been studied for many years and are being commercialized by Coskata.
Never underestimate the ability of microbes to scrounge a living from nearly any environment with water and energy available.

Tim writes:

I am a Canadian, here in the USA attending graduate school. Occasionally I hear hints in Michael Schmidt's language that he might be a fellow Canuck (words like "university" and "zed", and of course his impeccable class and intelligence). Michael, thinking back I'm not sure you've revealed anything about your past prior to your days in Indiana (at least not in the TWiMs I've listened to - I'm still working through them). If this is on purpose I respect that decision (I don't mean to pry into personal lives) - I was just curious.

Happy TWiMing!

- Tim

Juan writes:

Hi, i'm currently a Bioinformatics and Genomics Phd student at Penn State with a masters in Computer science and statistics. I'm currently working in antibiotic resistance in bacteria. I'm almost up to par with twim and i'm very grateful for your insightful discussions and the time you put in teaching everyone. This has been a great foundation for my microbiological knowledge. Keep up the good work.

I recently had the good luck to meet Dr Jo Handelsman during a distinguished talk here in my department.

I'm also a listener of twiv and twip, but not as often as twim.

Anonymous writes:

Last year, I started teaching microbiology for students interested in health-related fields. I caught up on all past TWiM episodes to help prepare me for teaching. I have learned so much from the podcasts, and so much what I already knew has been reinforced! In particular, the recent mention of conjugation experiments brought back happy memories, since I worked on a self-mobilizing pathogenicity plasmid for years. Listening to TWiM has an added benefit, since my students think I'm much smarter than I really am. :-)
I'm from another country and a few days ago, I was talking to a colleague (also from another country), and we discussed our shock when we first came to the US and found that everyone who works in health care can simply go home in their work clothes. In fact, they almost seem to wear their scrubs as a badge of honor (Do you see my scrubs? I do really, really important work!). It is my impression that many cases of nosocomial infections are associated with health care staff (consider that renovating an entire building wasn't enough to get rid of Klebsiella, which was probably brought back in on the first day of re-opening by the staff). The staff carry these bacteria, fungi, and viruses in their noses, on their skin, hands, and clothes around with them. They leave work, stop to buy groceries on their way home, pick kids up from daycare/school, and take their clothes home and wash them with the rest of their household laundry.....
In a number of other countries, health care personnel have to change in designated rooms at the facility. Their uniforms have their names sewn in, or embroidered on, stay behind at the end of the day, and are properly washed by the facility itself. Personnel can (and sometimes are required to) showers before they change into their regular clothes and leave the facility.
Maybe I'm missing some crucial piece of the puzzle, but it seems like a relatively inexpensive and effective way to limit spread of antibiotic resistant bacteria to the general community. It may also have a positive outcome on the spread within the health care setting. I would appreciate it, if anyone on the podcast could comment on this.

Tim writes:

Hello TWiMsters! (I apologize if you receive this message twice, I just noticed that you have a contact form for sending emails.) 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 link
s 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.

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.

Jennie writes:

Jennie Williams (RN) here - I've just seen something from Medscape that I thought you'd be delighted to know. An offering of clinical guidance on a successful recipe for Fecal Transplantation (bio-transplantation) for C difficile. Historical background on Fecal Microbiota Transplantation and a picture of success beyond C Dif to inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), idiopathic constipation as well. Fecal Transfer appears to work for C Dif that relapses as well.

Aside from fairly direct fecal transfers - this synthetic poo is described:
Elaine O. Petrof, MD, assistant professor, Department of Medicine, Infectious Diseases, Kingston General Hospital, Queen's University, Ontario, Canada, and colleagues created the human synthetic stool mixture by culturing the stool microbial diversity of a healthy 41-year-old woman and brewing a mixture of 33 different intestinal bacteria isolates in pure culture. They named the synthetic stool mixture RePOOPulate.

The bacterial mixture was infused into the colon of 2 patients in their 70s, both of whom were infected with a hypervirulent strain of C difficile, ribotype 078, and who had failed at least 3 courses of antibiotic therapy.

Both patients returned to normal bowel patterns in 2 or 3 days and remained symptom-free for 6 months. At that time, rRNA sequences representing the RePOOPulate mixture made up 25% of the gut bacterial population.

This link should get you to the right place.

Thank you once again for making the world safe for microbiota Vince and friends!

Yours with warmest regards

TWiM 61 Letters

Nate writes:

Hi my name is Nate. I am a senior in high school aspiring to become a microbiologist. I heard about this podcast through a class I took on biotechnology and have been listening for about 2 months. I really enjoy it and the other two shows even if I don't quite understand everything you talk about, but I grasp most things. So a few weeks ago I attended a biotechnology summer academy for high school students where we study one certain topic for three weeks with a professor at the college it was at. My subject was about the microbes that make up the stromatolites in the Great Salt Lake and why it's important that we understand it. I learned that they are made of Cyanobacteria and certain types of archea. The Cyanobacteria don't really make sense because they don't have a very high salinity tolerance, especially as high as the GSL which is 33% at parts of the lake. But yet they are there. I also learned that the rock is formed by the waste of the microbes which is calcium carbonate. These rocks have the potential to help with global warming. I'm not saying that I agree with the idea of global warming or not, but it is happening a little bit. So that brings up the question, Can we harvest and "grow" these rocks in a lab until they are big enough to put into the wild to "catch" some of the carbon dioxide in the atmosphere? I would like to hear your input on this subject as I didn't have a lot of time at the academy to study it. Thanks

[I asked Hazel Barton, here is her reply]

Actually this is a pretty good question and a number of folks have thought
about microbial CO2 sequestration in just this way.

Many of the carbonate rock deposits (limestone) from about 360+ million
years ago were formed during high periods of CO2, and we believe the CO2
was sequestered as rock by microbial activity. It dropped the atmospheric
CO2 levels and preserved it in a form that is obviously stable over
geologic time scales.

The problem we have today is the ion. To precipitate CO2 as carbonate,
you need a divalent ion. In the ancient oceans, there was plenty of
calcium around, so it was deposited as calcium carbonate (limestone).
Unfortunately, that easy source of calcium has been exhausted, so the
problem comes in generating the ion for the carbonate to precipitate. It
takes quite a bit of energy to do synthetically, so there's no net loss of
greenhouse gases. If someone could come up with a handy ion, generated
from a more passive process (such as decomposition in garbage), then we
could certainly sequester CO2 this way.

A good PhD project!

The stromatolite question is quite a bit more complicated and has to do
with the saturation index of carbonates in seawater when the CO2 levels
drop (from photosynthesis) - I can elaborate on that more if you need, but
the ion is still problematic.


Jim writes:

Hi guys,

This Google Plus community knocks off socks when just skimming through the photos/captions! Don't want anyone to overlook it.

Smithfield, VA

Robert writes:

In TWIM #60 @1:06:23 Michael Schmidt suggests that glucose for fermentation from biomass is a necessary step in production of fuel ethanol. Fuel ethanol and other low molecular weight compounds can also be produced by autotrophic anaerobic fermentation of syngas. Syngas is a mixture of carbon monoxide, carbon dioxide, and hydrogen produced by pyroclastic treatment of a wide variety of organic material including ligno-cellulose, recycled tires, sewage sludge, and natural gas or methane. These reactions have been studied for many years and are being commercialized by Coskata.

Never underestimate the ability of microbes to scrounge a living from nearly any environment with water and energy available.

Jesse writes:

Hello TWiM team! Thank you for the hours of entertainment and education you provide. I have a somewhat morbid question for you that's fairly random--I forget what inspired it exactly--but it has been bugging me: normally when an animal dies, it decays, but what happens if that animal is totally free from all microbes? So, what happens if a germ-free mouse dies in a sterile environment and no one disposes of it for a while? Does it decay somehow, or just dry out maybe?

Thanks again for all you do,

TWiM 60 Letters

Kelly writes:

I’m reeling from this episode!! The symbiosis, the web of life, the energies, chemicals, organisms of
evolutionary progression shaping our world naturally and by human intervention with unknown consequences, then you all tie it to the brain microbiome alterations affecting behavior! Yes!!!
A recent quote from a researcher says soon we’ll call our immune system the bacterial interaction system!
Yes! The microbes rule our world and us. God is bug. Oh the heresy!
This is what we see with inflammation therapy…bugs rule even if you can’t culture them with Koch’s postulates.
I have a Talmudic question:
If most alphaproteobacteria are phototrophic, and the brain doesn’t get sunshine, does vitamin D endocrine system dysregulation have an effect on their population in the brain?

Vitamin D hormone transcribes the AMPs to balance our bugs.
Why we use olmesartan to correct vitamin D dysregulation.
Angiotensin and Systems Thinking: Wrapping Your Mind Around the Big Picture

thank you!!

[the following email was sent to TWiP but I think TWiM listeners will like it]

Joe writes:

Vince and Dickson,

Here is a follow up on your biofuels question. To make fuels from crops succeed we need a biotech breakthrough that I really thought someone would have done already. Basically we need a bug that eats cellulose and converts it back to sugar so you can ferment it. Personally, I think there is a Nobel Prize in it for the group that creates an e. coli strain that converts cellulose to sugars. Once you have that, then you can feed the farm animals the corn and run your tractor on the corn stalks! Or you could use hay or grass clips or wood chips or waste paper, whatever is available cheaply. Until we get that bug, ethanol from corn will just be a niche technology.

People will keep pushing to use corn crops or other high sugar crops to make fuel, but the economics are not good and the lost opportunity costs are too high. Look how the modest current efforts in the USA have pushed up food prices and still required government subsidies to be competitive. No doubt there is a listener out there with lots of arguments for how great ethanol from corn is but I don't see anything like the margin needed to make it a viable market changing crude oil substitute.

I will show my age and tell you that as a senior chemical engineering design project in 1980 at Purdue, we looked at how to convert crop waste materials (like corn stalks) into fuel and it wasn't pretty. The only real way to break down the cellulose was to grind it up and treat it with hot fuming sulfuric acid in big reactors. Fuming sulfuric is 98% concentrated acid that is saturated with sulfur trioxide gas, brute force chemistry for sure! As I remember, you could get pretty good conversion of the cellulose, but the ugly part was separating the good stuff from all the waste acid and the non reactive lignin. Once you got all the acid out of the good stuff, then you still had to ferment the sugars. It is not surprising that you don't see anybody running this process to make fuel! We need a biotech solution to break down the cellulose without all the mess. I think folks were looking at the microbes in termites' stomachs as a place to start., but I have not heard of any progress on this in several years.

I will add that biofuels are not the only option for our fuel supply. For the past 100 years, we have had repeated dramatic reports that we are about to run out of oil and yet it never seems to happen! I remember a particularly detailed one in Scientific American about 10-15 years ago with beautiful graphs and everything. Each time the trumpets of doom sound, some smart engineer or geologist comes up with a new way to extract more oil. I don't see any reason why this trend will suddenly stop this time, we still have lots of tar sands, deep oil, and shale oil that have not been touched. Please note that I am not expressing a political view on the social correctness of these options just the technical aspects. Even more impressive are the reported quantities of frozen methane hydrate clathrates on the ocean floor that would likely be fairly easy to extract. Some estimates are that there is more than 10 times the amount of energy stored there than in all the oil we have ever used. Obviously none of these fossil fuels address the CO2 generation concerns that many people have.

Wind, solar, hydro and even nuclear power all have their places and I hope their niches keep growing as the technology improves, but nothing comes close to competing with chemical energy as a cheap, portable, high density source of energy. One just needs to look at biology to see the truth of this; plants fix the suns energy into chemical forms that then cascade through the food chain ever evolving into more complex forms. How cool is that!

Thanks for helping me stretch my brain each week! Thus ends "This Week in Chemical Engineering"!

Warmest Regards,

Joe Griebstein
EH&S Manager, LSG

Robin writes:

How about phage fossils?

Now that we know that phages have an apparently symbiotic relationship with mammals, is it too farfetched to imagine that some phages were once incorporated into - and expressed - in metazoa?

One line of research might be a search for such fossil sequences in the genomic databases that already exist. Perhaps someone is already doing it?

The reference to salicylates in my last email was prompted by Dr. Schacter's comment that methyl salicylate reminded him of acetylsalicylic acid, and to show how the acetyl group was important in the clinical effects of the latter.

Thanks for such thought-provoking and paradigm-shifting discussions!

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