Elio replies.
Nice to hear form you again, Paul. I guess surprise is about as subjective a term as there is, but you have a point.

Indeed the GFP fusion question was one we worried about. In the paper, we worked very hard to be sure that GFP was not the reason the protein was going to the poles. One of the best things thing we did (I think) was compete the polar foci away from the poles by expressing the wild type proteins without the GFP tag. Not only was each protein released from the poles in the presence of the wild type version, but each protein was competed away only by its own wild type, not by expressing the other protein (so the effect was very specific). Also, the original polar localization was determined by isolating polar membrane vesicles where only the wild type proteins were being made.

Amazing! It's a small step from there, to actually having something that will encode something that can be transcribed...and then the paradigm is broken, and the possibilities for having living systems that look nothing like ours, expand. Thanks!

Hi

Marvellous story. I wonder if the aminoacidic sequence of ArdA has this one repeated: Alanine-Asparagine-Aspartic (or in Spanish: Aspartico-Asparagina-Alanina) ;-D

Regards

Your blogs and information attracts me to come back again n again.

Your mother told you to wear a heavy jacket.

But really, H. sap. readily jumps to new environments, and the pelts of whole ecosystems hang from our collective belt.

that was a outstanding article very informative i really enjoyed reading it thanks

The Christmas Island rat is thought to have succumbed to a protozoan that was infecting introduced black rats.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0003602

Interesting, but isn't there evidence that a lot of GFP fusions show artifactual polar localization? I'd be skeptical of TnaA, a cytoplasmic catabolic enzyme at high concentration.

Elio replies:
Thanks for the observation. A good point that the author may want to comment on.

It's all about ecology and evolution, even to physicians, I think. Medical Darwinism?

Thank you, Mr. Friedman, for a most interesting and inspiring post.

Phage therapy holds a great deal of promise for treating antibiotic resistant infections and I wish they were already in use for our most serious cases of MRSA, VRE, and other potentially deadly infections. Too many people are dying, and I think the benefits far outweigh the risks for someone with life threatening infections. In particular, if wound and skin infections can be treated early on with phage therapy, that would prevent them from being more entrenched and difficult to treat - I would think the immunogenic reaction would be low in such circumstances.

Offhand, how different is the management of a phage immunogenic reaction compared to managing an antibiotic-induced Jarisch-Herxheimer reaction? The lysin-deficient phage sounds like a fantastic solution to this problem and the others you mention.

This study on treating Pseudomonas in mice with phage was conducted by a company in Ireland of which I am not familiar - I hope to see them extend their research to human trials. I learned that not long ago a biosciences company, AmpliPhi, is conducting phage therapy clinical trials for human cystic fibrosis (CF) patients. See: http://www.ampliphibio.com/index.php/pipeline/product_pipeline

I'm wondering about the technical challenges which come with treating patients with CF and how the FDA would classify their treatment. How much strain variation is found within CF patients' lungs? My understanding is some phages can target one specific strain of bacteria, while others are effective on different strains. If patients have multiple strains, individualized phage "cocktails" may need to be employed that extend beyond the use of even two phages. With no standardized formula, wouldn't this be problematic for drug developers and the FDA? Or are patients' lungs colonized by strains which are the same resistant strains? Maybe phage therapy could be mass produced annually to keep up with evolving strains and treated by the FDA much as a flu vaccine would be?

Whether or not you'd call it 'art' is something some might question, but the New Zealand $50 note features a mushroom (pictures of the note at http://www.rbnz.govt.nz/news/2000/0088734.html). The mushroom at the lower right of the lower side of the note is Entoloma hochstetteteri; New Zealand currency has a long tradition of being decorated with illustrations of birds, and the bird on the $50 note is the kokako. The fungus is illustrated because its Maori name, werewere kokako, refers to the cap of the mushroom being the same colour as the wattles on the face of the bird (take a look at this).

What a great idea! I will enjoy exploring this site. What could be better that history, art and mushrooms? (besides history, art and bugs, that is!)

The Hawaiian Bobtail Squid very neat looking picture!

"…even in our worst circumstances we have always been a relatively
minor interest of the vast microbial world. Pathogenicity is not the
rule. Indeed, it occurs so infrequently and involves such a relatively
small number of species, considering the huge population of
bacteria on earth, that it has a freakish aspect. Disease usually
results from inconclusive negotiations for symbiosis, an
overstepping of the line by one side or the other, a biological
misinterpretation of borders.”

Lewis Thomas 1974

http://www.youtube.com/watch?v=uAJDD1_Oexo

Today’s Talmudic question makes me remember the old controversy about the bdellovibrios: Were indeed parasites or predators of the host bacteria they eventually used as substrate to grow and multiply? Since the bdellovibrios discovery by H. Stolp and the pioneering (1970-1980) work in the subject by M. Starr, M. Shilo, S. Rittenberg, R. Seidler and a few others, that question has been going around and surfacing now and then in the discussions.

Now this one goes to Marvine who asked: Does God ever answer?
Hummm… May be He answers using the “language of the facts themselves” so we may look at them, touch them, smell the, hear them, eventually “taste them”, and, above all, think about them in myriad ways… (I am not sure if the last paragraph will pass censorship.I'll understand it doesn't...).

Agree with Vincent Racaniello and Paula--why spend a whole lot of energy fighting when you can live in peace with your host by being useful? Eat, sleep and lounge around on your fimbrae and secrete a toxic chemical against your gracious host's enemies every so often. Or make a yummy nutrient. Now I'm not shifting human values onto microbes --or am I? Hummm. Maybe they've shifted microbial values onto us.

An answer from evlutionary game theory can be found in Nowak's paper
Five rules for the evolution of cooperation, and related work. I expect that non-pathogeny, simply getting along with your host without killing it, should be even easier to evolve, so I'm not surprised it did. I would instead argue that pathogeny could be a transient state in the co-evolution of bacterias and their hosts, which ends in either the extinction of one of the species involved, or non-pathogeny.

For what it is worth, I think folks have given some interesting and thoughtful answers to Elio's Talmudic Question here. It is very clear to me that, for both pathogens and mutualists, there exists a lot of "cross talk" between microbe and macrobe. So the concept of dysbiosis and probiosis (the holobiont made up of microbe and macrobe out of balance or maintaining balance) is relevant. In both cases, there is a delicate dance of signals and responses---in both directions---with an ancient history.

So it isn't simply that microbes see us as a surface; our epithelia tend to react to colonization. Perhaps this level of cross talk, with the evolutionary darwinnowing implied, is responsible for the small percentage of "microbial juvenile delinquents" (which get most of the press) observed.

As in one of Elio's earlier Talmudic Questions, a related question is why archaea have not been established (though there are some gray areas) as pathogens...because there are plenty of archaea in mutualistic associations with macrobes. It's not that (as one reader put it) "archaea don't eat meat." The mutualistic associations imply the same coevolutionary history under discussion. So why no frank pathogens?

Donne wrote that no man is an island. In a similar way, for good or for ill, we coexist with a microverse of prokaryotes...and are interacting incessantly. If only, as Joshua Lederberg famously wrote, we knew the frequency! Work continues, by wiser heads than mine.

Does God ever answer?

And, what really happens post-mating in senescent salmon and octopoda, pathogenically?

wow, who would have thought there was so much going on with bacteria!

More would I think if it were not for the immune response of a potential host organism. This relates to the above question as I guess this requires a lot of energy/specialised traits. However, viruses - if anything - put the increase of energy use on to the host and not themselves. So this shouldn't be an issue for viruses.

When microbes evolve with their hosts for long periods of time, they learn to get along. In symbiotic relationships there is no point in the microbe causing damage to the host, so it is negatively selected for during evolution.

I think it's because successful pathogenicity requires so much energy and specialized traits that it is not "the best world" for a microrganism.

If it has the possibility to live in a "free" way, it will engage this form of life...

Anybody has any other idea?

If the molecular folks still have to point out limitations with every study they publish, even though these are well known by now, I think the culture-based studies should do the same. For instance, they have been culturing Pasteurella out of sheep's noses for decades and still can't decide whether they kill bighorn sheep. Meanwhile, molecular evidence has surfaced that suggests many other microbes are involved. Completely ignored of course.

And in the indoors, should we just stop studying it because some people get freaked out? Is that the fault of the scientists? Should me not learn what is there, what has been there outside of what we can grow? Can we not be interested in how things move around indoors where we spend 90% of our time?

The real nonsense of this blog is the statement that we should ONLY care when an outbreak of something we understand happens (e.g. Clostridium). Well what about the 100,000 deaths per year due to infections acquired in hospital? These are mostly opportunistic. Where did they come from? How can we stop them? Are surfaces involved? Do the bugs come on clothes from the restroom? Do we know this already? Most of the time, these agents are not identified.

DNA work is a wonderful compliment to what is known already in microbiology. It has expanded our understanding 1000-fold over culture methods in the natural world. It has the potential to do the same in the built environment. Please keep this in mind.

Elio replies:

Let’s first agree about the obvious. When it comes to environmental samples, plate counts only detect the bacteria that can be readily cultivated. This widely recognized and is called the “Great Plate Count Anomaly.” Thus, plate counts severely underestimate the number of species in a sample. Plate counts reveal the presence of only some of the living bacteria in the sample and usually tell of their abundance.

On the other hand, metagenomic analysis of a sample tells us what DNA is present and potentially which genes are in attendance. This is indeed valuable information, as it suggests the biological potential in a sample. It is far more inclusive but, generally speaking, is only suggestive. Unless specialized techniques are used, it does not provide quantitative information, nor does it distinguished between live and dead organisms. Relevant to the paper in question is that many human-associated bacteria die rapidly on drying, although the DNA remains in their carcasses.

It would seem obvious that both approaches should be used in concert, being that they yield different kinds of information. Alas, this is seldom done, as many workers favor one of these approaches over the other. They ought to complement each other. To use an imperfect analogy, think of a large library. A metagenomicist may know the titles of the books, usually with a small amount of information about each, the “cultivator” will have read a few of them.

I suspect that Scott may agree with these general points. He says, with plenty of reason, that everyone should be mindful of the limitations of their studies. It’s true that the plate anomaly is seldom spelled out, but I believe that most people are more aware of the limitations of cultivation techniques than of metagenomics.

Merry replies:

I envy you, Charli! Such fascinating phenomena to explore, and you are poised to do just that. I can't really answer your questions as my knowledge of VAPs is strictly 2nd hand from reading some papers and writing up a blog post. You are already a bit ahead of me. I can, and will, offer a couple of comments.

First, you are wondering whether viral assembly is necessary for triggering opening of the VAPs. I suggest you might find some hints in the 2011 paper by Snyder & Young: Potential role of cellular ESCRT proteins in the STIV
life cycle.
Biochem. Soc. Trans. (2011) 39, 107–110; doi:10.1042/BST0390107

As to the IPBs, I know only of that same paper. The authors would seem to be your best option for more info on that.

Thanks for the inquiry and I hope your hypothetical research project yields some interesting hypotheses.

One of the challenging bits regarding both "life on other worlds" and "how life evolved here on Earth" is that we only have one example that seems pretty successful here and now to study.

Joshua Lederberg used to push for looking for "life as we do *not* know it." Not easy (I liked his 1960s suggestion of enrichment culture in the presence of many curies of 32P...which might enrich for things like Deinococcus in retrospect). Anyway, I am always on the lookout for "weird" biological facts that might shed light on these biophilosophical questions.

One of my favorites is the much-missed Tracy Sonneborn's "cortical inheritance" concept in Paramecium. That is, a prior structure is used as a "blueprint" for the new structure (you can see me shielding my eyes from the Intelligent Design people). I could see things like simple proteins or nucleic acid polymers acting in a similar fashion.

http://en.wikipedia.org/wiki/Cortical_inheritance

My best guess is that "early life" was pretty slow and inefficient. Or else it is still hiding out here on Earth, waiting for someone cleverer than yours truly to find it!

The fluid mechanics theory is really amazing, and thank you very much for explaining it.

We must imagine these fragile bags of chemicals conjugating and splitting by mechanical agitation, much like soap bubbles. Perhaps the beginning of cellular life and Darwinian evolution would not be the chaotic RNA production in the open ocean, or even within the membranes, but the accumulation of lipids to extend this microenvironmnent -- or even of defenses against too-promiscuous conjugation.

In this sense, RNA, proteins, DNA, and all the rest are just the primordial membrane's way of making more membrane. That membrane has since succeeded in making quite a lot of itself.

Elio adds:
"Omnis membrana ex membrana." (Blobel 1980, http://www.pnas.org/content/77/3/1496.full.pdf)

first comment
on the above;it seems the commenter has misunderstood the text published in here. The above first commenter is saying the same what is published in here correctly.

]]> Wed, 04 Apr 2012 12:27:34 -0700 http://schaechter.asmblog.org/schaechter/2009/11/fiv-1.html#c6a00d8341c5e1453ef0168e9a5a640970c http://feedproxy.google.com/~r/STCcomments/~3/sFJeidsxe3M/the-janus-bug.html There are more than 200 known diseases transmitted through food. Many of these diseases could originate at the farming and processing level. Food-borne illness can also result from temperature abuses, undercooking or cross-contamination by food services, restaurants and home preparation. Bacteria related food poisoning is the most common, but fewer than 20 of the many thousands of different bacteria actually are the culprit 6a00d8341c5e1453ef016303a17c82970d@http://schaechter.asmblog.org/schaechter/ ilcmicrochem:

There are more than 200 known diseases transmitted through food. Many of these diseases could originate at the farming and processing level. Food-borne illness can also result from temperature abuses, undercooking or cross-contamination by food services, restaurants and home preparation. Bacteria related food poisoning is the most common, but fewer than 20 of the many thousands of different bacteria actually are the culprit


]]> Tue, 03 Apr 2012 03:40:51 -0700 http://schaechter.asmblog.org/schaechter/2011/08/the-janus-bug.html#c6a00d8341c5e1453ef016303a17c82970d