Microbes Make it Snow

1 Feb

This post was chosen as an Editor's Selection for ResearchBlogging.orgThe recent snow and ice, and deeper snow, and even more ice, across much of the U.S. over the past few weeks have finally inspired me to put together my first post for the new year.  You’re probably wondering how on earth microbes have anything to do with the 3 feet of snow you had to dig your car out from under last week…  

…but hear me out.

Blowing in the wind

I have two “believe it or not” statements for today: First, believe it or not, microbes are ubiquitous in the Earth’s atmosphere (Bowers et al. 2009, and others).  “Ubiquitous” is a fantastic word that simply means “absolutely everywhere” and it’s especially true with microbes.  As a soil microbiologist, I immediately think of soils and sediments all over the globe and the wide array of fungi and bacteria that keep the planet green (and purple and red and brown), and it makes sense because there are so many things to eat in soils.  There’s a never-ending supply of nutrients from dead and decaying plants, worms, insects, other microbes, and even weathering rocks.  But I also know that out in the open ocean microbes are abundant and provide the foundation for the food chain, not to mention nutrient cycling and overall marine ecosystem health.  We’ve known these things for quite some time now (hence, my “microbe-centric” view of life). Our Microbial Planet Poster

What doesn’t always make sense to a terrestrial biologist is that microbes are also extremely abundant in the air around us, above and beyond our reach, floating in the breeze and being carried thousands of miles on trans-oceanic trade winds.   It’s true, though, and for years we assumed that these microbes must be in a sort of hibernation mode, because there’s nothing to eat, harsh conditions often including extreme dryness, cold temperatures and powerful UV radiation from the sun.  More recently, however,  we’ve begun to understand that only a portion of these airborne microbes are hibernating, while others remain active, usually bound in soil particles or cloud droplets (Sattler et al. 2001).  And as long as these little guys are metabolically active, they have the potential to make changes to their environment, even in the atmosphere.

Ice, Ice, Baby (sorry, I couldn’t help myself)

Which leads me to my second “believe it or not” statement for the day:  many of those atmospheric microbes have been found to nucleate ice (Bauer et al. 2003).  What I mean by “nucleate ice” is that they can serve as the starting point for ice crystals to begin to form.   What makes this really cool (pardon the pun) is that ice-nucleating microbes have been found to make specific proteins on the surface of their cells which catalyze the formation of ice crystals at relatively high temperatures.  This action not only allows the crystals to form outside the microbe, rather than inside where ice crystals would damage cellular membranes and kill the microbe, but the formation of these crystals also releases very small amounts of heat energy, keeping the microbe that much safer from freezing. 

Commercial snow-seeding material.

Commercially available snow-seeder.

You might have heard about these guys (indirectly) before if you’ve ever heard of “cloud seeding.”  There’s a commercially available freeze-dried preparation of ice-nucleating bacteria that many ski resorts will shoot up into the clouds to help encourage snowfall.  A slightly less well-known practice is the application of “ice-minus” bacteria to reduce crop loss due to frost.  In that case, growers have taken advantage of specific mutant bacteria which lack the genes for the ice-nucleating protein and spray these bacteria across the foliar surfaces so that ice won’t form as easily.  The idea here is that ice-nucleating bacteria are very commonly found on plant surfaces, and can lead to frost damage.  But those lacking the gene (called “ice-minus”) when applied to the plants, outcompete the natural bacteria, and reduce the formation of frost on plant surfaces.   

Atmospheric Microbes = Snow

How bacteria make up snowflakes.

Bacteria and snowflakes.

But these ice-nucleating bacteria exist all over the world, in the soil and in the air around us and may be affecting more than just the ski slopes and strawberries.  A very interesting study by a group of scientists out at the University of Colorado in Boulder recently looked specifically at ice-nucleating bacteria and how microbial abundances in the atmosphere may alter atmospheric conditions (Bowers, et al 2009).   In order to address this question, they took a number of air samples from the Storm Peak Laboratory at the top of Mt. Werner near Steamboat Springs, CO.  Their air samples contained over 640 different bacterial species (via genetic sequence), but their data indicated they did not even begin to sample the full diversity of the airborne microbial community.  Despite variable weather conditions during sampling, the total airborne microbial numbers remained stable and didn’t change throughout the sampling period.  However, with increasing relative humidity, there was a significant increase in ice-nucleating bacteria.  They found that the abundance of ice-nucleating bacteria was significantly greater in cloudy air samples, than in clear (or non-cloudy) air samples.  They even suggested that some bacteria may be able to respond to favorable (humid and cloudy) conditions and adjust their concentrations of ice-nucleating proteins, consequently increasing the ice-nucleation potential of these species.

Take-home message…

So, what does all this have to do with the massive downfall of snow and ice this season?  Well, as much as I love to blame global warming for more extreme weather events, we don’t have to connect a whole lot of dots to be able to believe that atmospheric microorganisms may be playing a role as well. 

The more people we have on the planet, the greater population densities become, and the more disturbance we cause to land surfaces, the more soil, dust, particulate matter, bacteria and fungi rise into the atmosphere and interact with our weather patterns.  Much the same way that cloud seeding works, it seems our activities down here are affecting the number of microbes and consequently cloud formation (bioprecipitation, if you will) up there.

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Bauer, H., Giebl, H., Hitzenberger, R., Kasper-Geibl, A., Reischl, G. Zibuschka, F., and H. Puxbaum. 2003.  Airborne bacteria as cloud condensation nuclei.  Journal of Geophysical Research, 108:4658.

ResearchBlogging.orgBowers, R., Lauber, C., Wiedinmyer, C., Hamady, M., Hallar, A., Fall, R., Knight, R., & Fierer, N. (2009). Characterization of Airborne Microbial Communities at a High-Elevation Site and Their Potential To Act as Atmospheric Ice Nuclei Applied and Environmental Microbiology, 75 (15): 5121-5130 DOI: 10.1128/AEM.00447-09

 

Griffin, D.W. 2004.  Terrestrial microorganisms at an altitude of 20,000 m in Earth’s atmosphere. Aerobiologia, 20:135-140.

Sattler, B., Puxbaum, H., and R. Psenner. 2001.  Bacterial growth in super-cooled cloud droplets.  Geophysical Research Letters, 28:239-242.

The Trouble With Triclosan

1 Dec

Just a few products you might find Triclosan in.

An article was released online Monday in Environmental Health Perspectives which surprised me. For the last five or six years I’ve been enthusiastically extolling the evils of triclosan in the environment, but the connection with human immune dysfunction really caught me by surprise, most likely because I’m a microbiologist (this is probably not news to all you toxicologists out there). As someone who suffers both indoor and outdoor allergies (including hayfever) as well as allergy-induced asthma, it’s no small thing for the authors to be able to say with such a level of confidence…

“… higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hayfever (p<0.01).”   Clayton, et al., 2010.

The mechanism of impact on the human immune system isn’t clear yet, but in reading the article I discovered that triclosan has been associated with not only endocrine disruption, but also central nervous system effects and thyroid problems for several years now.

This knowledge becomes particularly disturbing when you consider the fact that since it’s creation in the 1960’s, triclosan (also known by its more descriptive chemical name: 2,4,4’-trichloro-2’-hydroxydiphenyl ether) has been added to countless consumer products as an antimicrobial and preservative, including but certainly not limited to: hand soaps, laundry detergents, toothpastes, wound disinfection solutions, deodorants, facial tissues, plastic kitchen utensils, medical devices, and toys.

If a product’s label says “Antimicrobial” you can bet it contains triclosan or a triclosan derivative. Do a quick literature search and you’ll find we’re discovering new uses for it every month, incorporating it into plastics and personal care products of all kinds. Consequently, triclosan and its derivatives are now found in the urine and tissues of over 75% of all Americans, and in soils, sediments, and waterways all over the world.

Enter, environmental microbial populations.

What you might be thinking is that since triclosan is added to things for its antimicrobial properties, it must be wiping out hordes of bacteria and fungi, reducing their numbers worldwide… well, not exactly.

Some bacteria are naturally resistant to triclosan, like certain Pseudomonas species, while in others it actually causes mutagenesis (directed mutations) of their already existing resistance factors. What that means, is that bacteria have already developed a way to resist or survive a number of toxins, like heavy metals or salts, and when they are exposed to triclosan, their resistance factors actually adjust to treat triclosan in the same manner.

A great example would be common bacterial efflux pumps; these are mechanisms within the cellular membrane designed to “pump” a specific toxin right back out of the cell, where it can’t hurt the bacteria. When a bacterium is exposed to triclosan, these pumps go into over-drive and begin to pump out anything that remotely resembles an antimicrobial or antibiotic.

The tripartite efflux pump of Salmonella, which pumps out antibacterial drugs to foster multidrug resistance. Image: Cambridge Dept of Pathology.

There could hardly be a better use for the old adage, “What doesn’t kill us, make us stronger.”

 This type of triclosan-induced antimicrobial resistance has been proven in model species like E. coli, Salmonella enterica, Staphylococcus aureus, and Mycobacterium tuberculosis, but to date it’s been uncertain if these same effects are true of environmental species (common soil and water bacteria). Pycke, et al.(2010) set out to answer that question and their work was published in a recent article in Applied and Environmental Microbiology.

I guess the good news from their work would be that the species of environmental bacteria the authors tested (Rhodospirillum rubrum) was fairly sensitive to triclosan, and the concentrations needed to inhibit its growth and even kill this bacteria were similar to some of the most sensitive species that have been tested to date.

What this means to you: when you use an antibacterial soap to wash your hands, you’re probably killing off 90% of these types of bacteria on in your hands, i.e. they are very susceptible to high concentrations.

The not so good news is that under low-levels of triclosan exposure, the very same efflux mechanisms that I described above were able to confer resistance to these bacteria, and not just to triclosan, but also to a wide range of antibiotics including tetracycline, chloramphenicol, fluroquinolones, and others.

What this means to you: after you wash your hands with antibacterial soap, and that triclosan is diluted in water and washed out into your septic or local waste-water treatment plant, the environmental bacteria exposed to lower levels of triclosan are not killed, but essentially “turn on” their efflux pumps and become resistant to some of the most common antibiotics in use.

We used to think that a bacterium had to first be exposed to a specific antibiotic in order to become resistant to it (or at least one of his pals was exposed and passed on the genetic resistance); now we know that our own waste-streams, laden with chronic levels of the very antimicrobial products our culture clings to, are fostering even greater levels of antibiotic resistant bacteria in the environment.

To sum up

Two reasons not to buy or use products with antimicrobial chemicals like triclosan or triclosan derivatives:
1.) Increased incidence of hayfever, allergies, and immune dysfunction;
2.) Decimation of the human race by antibiotic resistant diseases. (ok, maybe that’s a little overblown, but you get the idea)

If the one doesn’t make you think twice, surely the other will.

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ResearchBlogging.org
Clayton, E., Todd, M., Dowd, J., & Aiello, A. (2010). The Impact of Bisphenol A and Triclosan on Immune Parameters in the US Population, NHANES 2003-2006 Environmental Health Perspectives DOI: 10.1289/ehp.1002883

Pycke, B., Crabbe, A., Verstraete, W., & Leys, N. (2010). Characterization of Triclosan-Resistant Mutants Reveals Multiple Antimicrobial Resistance Mechanisms in Rhodospirillum rubrum S1H Applied and Environmental Microbiology, 76 (10), 3116-3123 DOI: 10.1128/AEM.02757-09

Fungi that eat lead

19 Nov

This post was chosen as an Editor's Selection for ResearchBlogging.orgBioavailability = solubility (for the most part)

To discuss heavy metals (lead, nickel, mercury, cadmium, silver, copper, and so on) and how they can be detrimental to the environment or toxic to people, plants, or animals, we have to first posses a vague understanding of bioavailability and bioaccessibility.  These terms describe whether or not the substance in question can cross an organism’s cellular membrane, which allows the organism’s internal system access to the substance.

This might sound a little confusing at first, but if the toxin can’t get inside the organism, it can’t do damage (i.e. if the small child didn’t eat the paint flakes, he wouldn’t suffer from lead poisoning).  Whether or not a toxic heavy-metal can enter into the cells of a plant, microbe, and even a human, depends on the solubility of that metal, and the solubility of any given metal will change according to what it’s chemically bound with. For an entertaining visual demonstration of chemical bonding, I thought you might enjoy this video …

But seriously, bioavailability…

The child eating lead based paint is actually a good illustration of what I’m trying to convey here.  The lead typically found in lead based paint is lead carbonate or lead chromate, which means the lead is chemically bound with carbon and oxygen, or chromium and oxygen.  Humans cannot absorb that type of lead through our skin and therefore it isn’t toxic unless ingested, in which case our digestive processes dissolve the different lead-compounds and we absorb the lead into our systems.

However, lead nitrate is another story altogether.  In lead nitrate, the lead is bound with nitrogen and oxygen and is extremely toxic because it is highly soluble in water; we can absorb it through our skin fairly easily, so we don’t have to eat it for it to become bioaccessible.

Most of the time, bioaccessabilty and bioavailability, relate directly back to the solubility of a substance.  If it’s not soluble, it’s not bioavailable, and vice versa.  The more bioavailable a toxin is, the more dangerous it is, to us and the environment at large.

But what about the microbes…?

With all that in mind, I find it particularly interesting to know that various microorganisms found in the soils, sediments, and waters of contaminated sites (mines, smelters, spill sites, etc.) have been discovered over the last 50 years capable of converting insoluble metal compounds (such as lead carbonate) into more soluble forms.   These microbes are able to convert metals from relatively inert forms into readily available (often bioavailable) forms and have received much attention for their biotechnological applications, such as dissolving useful metals from metal ores (termed “bioleaching”).

In fact, in 1995, Geoffrey Gadd and his colleagues at the University of Dundee (Dundee, U.K.) developed a particularly useful method to screen soil fungi for their potential ability to solubilize heavy metals in the lab (Gadd et al, 1995).  They were able to incorporate any one of a variety of insoluble metal compounds into the agar of a Petri dish and measure the rate at which the fungus could dissolve the metals.  They tested the method using aluminum, cobalt, manganese and zinc and found many fungi from a common “garden soil” sample were able to dissolve insoluble zinc and cobalt just as quickly as they could grow and expand across the Petri dish.

A common fungus dissolves the highly insoluble lead carbonate as it grows across a Petri dish.

In my own experiments recently, I’ve tested this method and have a nice photo of a fairly common fungus (Aspergillus niger) literally dissolving lead carbonate, just like the lead carbonate found in lead-based paints. (photo at right)

This may initially seem like a bad thing… soil organisms turning relatively insoluble and inert metals into the more soluble, and consequently more bioavailable, forms.  But learning about the natural process and understanding how it all works actually affords science a new and developing tool in the ongoing struggle against contamination.  We can apply our knowledge to clean up efforts and remediation work on contaminated sites, and even biotechnology for lower-impact mining techniques.

Of course, we have a long way to go with the organisms I’m working on right now, but along the way they help us understand which contamination sites can cause the most dangerous types of human exposure and why.  It all comes back to how the toxins interact with the microbes in the soil!

So, back to the lab I go this afternoon to see how my other fungi are breaking down lead (or not) and converting metals from insoluble forms to the bioavailable forms (after I watch that chemical bonding video one more time for laughs!)

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ResearchBlogging.orgSayer, J., Raggett, S., & Gadd, G. (1995). Solubilization of insoluble metal compounds by soil fungi: development of a screening method for solubilizing ability and metal tolerance Mycological Research, 99 (8), 987-993 DOI: 10.1016/S0953-7562(09)80762-4

10 Questions You Should be Prepared to Answer in a Science Faculty Interview

18 Nov

It’s pretty clear from the frequency of my posts (or lack thereof) how things have been going in the lab lately.  When things go swimmingly, I time-manage effectively, plan my experiments efficiently, and have time for the fun of science-writing.  When things don’t go so well, experiments get backed up, countless hours in the laminar-flow hood are followed by countless hours plying the PCR gods with gifts and trinkets, and by the time I done with all that, I’m too exhausted and brain-dead to even enjoy writing.  So, today I’m taking my lunch break to make a slight departure from my norm, just to get posting again.

After some discussion with a number of other newby postdocs in my field, it’s become apparent that many of us are (more or less) completely unprepared for what is hopefully the inevitable: a serious interview for a faculty position.   More specifically, a tenure-track faculty position at a research institution.  I’m not saying we’ll all go that direction, but many of us will and it pays to be prepared in the event of that oh-so-coveted interview.

I’ve done a number of online searches, as have my colleagues, on precisely how to prepare for such an interview and the results have been woefully vague, ambiguous, and decidedly unhelpful in the real world. 

Many of the questions you’ll find after such a search are similar to those you might find on any help site for any type of job interview…

  • Why are you interested in this position?
  • How do you see yourself contributing to this institution?
  • What is the biggest conflict you have ever been involved in at work? How did you handle the situation?
  • (my personal favorite) What do you consider to be your greatest weakness?

Other questions you might find even on site specifically for faculty interviews largely revolve around describing your pedagogy and how you involve your students in your research… 

  • What kinds of research projects/topics could you pursue here?
  • What pedagogical changes do you see on the horizon in your discipline?
  • What courses have you created or proposed in the past five years?
  • How do you engage students, particularly in a course of non-majors?

 

Of course, you should by all means be prepared to answer these types of questions.  But having served (as the student member) on two search committees for science faculty positions, I noticed a slightly different and much more specific set of questions being asked at every single interview we conducted.  I discussed this recently with a colleague who had just completed an interviewfor a competitive science faculty position, and he confirmed having been asked a very similar set of questions. 

 So, I’ve included the basic questions here (in no particular order), with suggestions on how to answer, for the benefit of all those research-faculty wanabees out there that could use a heads up..

1.  What do you propose to study?  

Sort of an obvious question, but specificity is of import in your answers.  Specific examples of your key objectives, any possible or previously established field sites you’d like or plan to work on, methods you’ve applied in the past and that you’d like to apply in the future.  Think about how all this will fit in the department for which you’re interviewing, equipment and resources you could share, etc.

2.  Where will you submit your first/next grant proposal?

Again, specificity is what they are looking for.  They want to know that your work has a funding home, and that you have a precise idea of where that is, i.e. which programs within which agencies and what the deadlines are for proposals.  The flip side to this question is “To which journals will you submit your research for publication,” although I think this question is less important if you already have a strong publication record.

3.  Who will you collaborate with?

This is a 60/40 question as far as what I’ve seen… they want about 60% of your answer to be in-depth with regards to the other faculty within and around the institution, but 40% of your answer needs to include collaborators around the world (usually around the U.S. will suffice, but it depends on where you’re interviewing).  Ideally, you’ve had some experience with at least a few of these folks in the past or perhaps during the course of the interview and can feed off prior conversations with them.  And I can’t stress specificity  enough… name names folks, and toss out project ideas.

4.  What courses can you teach or would like to teach?

This often will also incorporate issues of pedagogy, including how you intend to engage your students, general teaching and testing philosophy.  Lets face it, though, teaching  is not usually a deal-breaker at most research institutions.  Show that you’ve given this some thought and they’ll probably be happy.  If you’ve taught before, mention the courses.  If you haven’t, take some time to look through the department’s course catalog, get a feel for what they already offer and where your expertise might be able to fill a gap. Again, be specific as possible, give course names and topics.

5.  How many students will you have/mentor (initially and beyond)?

This question and the next few all have to do with the structure of your desired/planned lab and research operations.  Think it through in detail before your interview and give your rationale with your answer.  Do you prefer to start with a boatload of people on board so that you can get all the research underway and publications rolling out?  Or do you think you’d only like one or two to begin with, then gradually increase to a maximum of x?  Why?

6.  Do you need/want a technician?

This is where you get to debate (before the interview, preferably) the virtues of a technician versus a postdoc or graduate student(s).  What would someone in each of these positions be responsible for and how does that shape the lab-legacy you hope to become your own?  And where would the funds come from for any or all of these types of positions?  What gives you the most bang for your buck?

7.  What equipment do you need?

Again, be specific.  Brand names, models, functions.  Multipurpose equipment is always a plus, but (obviously) there are techniques which require highly specialized equipment.  If that’s the case, would you be willing to offer a fee-based-service with your fancy-schmancy equipment to help recoup any financial investment the department may have to make?

8.  Estimated startup money?

This is something I’m not particularly good at, but I would say “aim high” and it’s been suggested that (depending on the size of the institution) you have to say at least $200k or you won’t be taken seriously.   In many cases, this won’t even come up until the job offer has been made, thenyour negotiation skills come into play.  However, this is something that’s definitely worth taking a pen and paper (and calculator) to before the interview.  Figure what you think you would need for the first two-five years, while you work on generating preliminary data and writing proposals, then add at least 25%, and you should be covered. 

9.  How many square feet of lab space do you need?

I’ve never seen this question posed in an interview before, but my colleague was asked this during his interview, so I’ve included it.  Have a rough idea of space needed and how you would set up your lab, considering efficiency as well as safety regulations.

10.  How much office space for yourself and students?

This relates strongly back to #5 and #6 (and even maybe #9 – depending on how much time you’ll spend in the lab versus your office), but also to what you have seen around the institution with regard to what everybody else has.  I hope this is a no-brainer:  Don’t say you need 300 ft2 of office space for yourself if everybody else there has about 100 ft2

In short, if it’s a job you really want, spend some serious time preparing to answer questions with specific, and well informed answers.  Every institution will be a little bit different in their focus and desires, but from their website, the job announcement, and the search committee, you should be able to get a feel for that before you ever show up for the interview.

I’d love to hear if anyone out there has had similar or vastly different experiences and how it all went down.  Let me know if I left something critical out, too!

Happy hunting!

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Many thanks to those whose interview experience helped shape this post!

How does your garden grow?

19 Oct

For a leaf-cutter ant, the answer to that question is not so much “silver bells and cockle-shells” as it is “one nutritious fungus and a variety of beneficial bacteria.”  It may not exactly be the stuff of nursery rhymes, but it’s certainly a fascinating three-way mutualism that makes for a great lesson in microbial ecology, and ecology in general, for that matter.

Leafcutter ant fungus-garden in a lab nest. Source: © Alex Wild 2010

Fungiculture, as it’s called, involves production of food or medicine by cultivating mushrooms or other fungi .  In the insect world, fungiculture is practiced by ambrosia beetles, termites, and gall midges, in addition to leaf-cutter (or attine) ants.  That’s right, millions of years before humans even thought about any type of agriculture, these insects evolved the ability to grow fungi for food (Mueller and Gerardo, 2002). 

Attine ants grow their fungal gardens in underground caverns or chambers and supply the fungus with leaf fragments from live plants collected aboveground.   They literally “feed the fungus” and in return, their larvae are reared exclusively on the fungus itself.  So, the ants provide the fungus with food, protection, and dispersal (fungal spores remain viable within the ant digestive tract and can be deposited via ant dung during the daily travels) while the fungus provides a high-quality food source with increased nutrition and survival for the ants. 

Much like humans, these insect farmers have become dependent on cultivated crops and have even developed task-partitioned societies.  And, just like our crops, theirs can be wiped out by parasites and pests (nematodes and mites), their harvest ruined by weeds and disease (unwanted/harmful fungal species), which can lead to collapse of the colony.  

To protect their fungal gardens, the ants have developed specialized behaviors like grooming and weeding the fungus, as well as producing their own antimicrobials through gland secretions, as well as large-scale application of weed killers.  Only, in this case, when I say “weed killers” I’m not talking about synthetic chemicals like RoundUp, I’m talking about specialized soil bacteria which produce potent antimicrobial compounds with specificity towards the unwanted fungal species.  (Barke, et a.l 2010). 

It’s long been known that the reproductive females in each colony pass on the fungal cultivar, but only recently have we begun to understand that the ant’s gardening toolbox is constantly evolving.  Along with the fungus, the queen also passes down at least one species of bacteria (a Pseudonocardia).  This particular bacterium produces an antifungal compound, specifically aimed at reducing the most common pest of the fungal gardens but which leaves the crop itself untouched.  But beyond that, the gardening ants also pick up a variety of soil bacteria along the way including Streptomyces.   In other words, each of the bacteria makes a unique antimicrobial compound that the ants use to their advantage in their agriculture depending on the particular pest the ants are challenged with.

To recap… 

We have leaf-cutter ants, going out into the world each day, chopping down entire forests so they can bring the good stuff home to feed their fungus.  The ants survive off this fungus, so it’s carefully cultivated and passed on from generation to generation, and they have specialized farmer-ants who will each spend their whole life tending to the fungal garden.  Some of the most important tools these farmers use to keep the fungus healthy and productive include natural soil bacteria.  For the worst pests they use a special bacteria, which was also passed on through the generations, but for more common pests, they can use a variety of bacteria collected from their surroundings: different tools for the different problems. 

So, when I hear  “Mary, Mary quite contrary, how does your garden grow?” I, for one, imagine colorful underground mushroom gardens with their little ant-farmers in their little ant-overalls walking the rows, killing weeds with soil bacteria (kinda like the doozers on Fraggle Rock, but with mushrooms). 

Is that weird?

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ResearchBlogging.orgBarke, J., Seipke, R., Grüschow, S., Heavens, D., Drou, N., Bibb, M., Goss, R., Yu, D., & Hutchings, M. (2010). A mixed community of actinomycetes produce multiple antibiotics for the fungus farming ant Acromyrmex octospinosus BMC Biology, 8 (1) DOI: 10.1186/1741-7007-8-109

 
Mueller, U. (2002). Fungus-farming insects: Multiple origins and diverse evolutionary histories Proceedings of the National Academy of Sciences, 99 (24), 15247-15249 DOI: 10.1073/pnas.242594799

Some yogurt each day keeps the doctor away

8 Oct

Health Benefits of Yogurt

There’s a great deal of debate these days about the sometimes wild and often wondrous health claims touted by the probiotics movement.  These special beneficial bacteria (mostly lactic acid bacteria like those found in yogurt, and available now it the convenient pill or capsule form) are claimed to not only cure everything including digestive disorders,  irritable bowel syndrome, pediatric asthma and allergies, but are also said to be capable of preventing a wide variety of problems including acne, eczema, vaginitis, halitosis, and even cancer.  Those skeptics (realists?) among us realize this is most likely impossible. 

I, of all people, would love to believe that just hand-full of species of beneficial bacteria, when ingested on a regular basis, can make the sick well, heal our wounds, lower our blood-pressure, and bolster our immune systems, but that’s the stuff of science-fiction fantasy and all rather outlandish. 

Or is it?

I posted a few weeks ago about a clinical trial using lactic acid bacteria (like those found in yogurt) to help mice stave off flu symptoms and found I had unwittingly placed myself on the side of the argument with the “snake-oil salesmen” and moneymakers (aka, commercial probiotics salespeople).  I do love to play devil’s advocate on occasion, so I began looking into the subject a bit more… where do all these various and sundry health claims come from? Are skilled marketing strategies simply playing on the human desire for a cure-all, a fountain of youth, or is there some seed of legitimacy at the base of it?

Probiotic Bacteria

On my quest for truth, I found first, the report by the American Academy of Microbiology, “Probiotic Microbes: The Scientific Basis”… a must-read for any truth-seeker on this subject.  However, since the time it was put together (November 2005), the myriad of health claims being made in the media (as well as the backlash against) has vastly expanded, and science did not have a grasp of precisely how this all worked within the human body. 

Which brings us to my second discovery in my quest: a truly seminal research study which (finally!) very clearly indicates how probiotics modulate human cellular pathways to achieve several varied, and perhaps unexpected, health benefits.  The article by van Baarlen and colleagues (full citation below) was actually published online in the Proceedings of the National Academy of Sciences the same week I made my original post on yogurt bacteria (Sept 7, 2010).

The study involved seven healthy, non-smoking adult human volunteers and the transcriptional responses (meaning, which genes were being actively expressed) of their stomach mucosa to consumption of live cells of Lactobacillus acidophilus, L. casei, L. rhamnosus, or a placebo control.    Every volunteer was exposed to each of the four treatments, with a two week break, or rest period, between treatments. 

The first discovery was that the gene expression profile of each of the volunteers was considerably different, regardless of treatment.  Of course, this reflects the fact that we are each individuals and our health and well-being is a sum of our genetic make-up, our environment and experiences.  But the implications are clear when we consider the conflicting results of many of the probiotic clinical trials.  Natural variation of genetic expression between individuals is high enough to mask the observed clinical effects in some people while not in others, especially when combined with the different effects of each bacterial species. 

This brings me to the second major discovery: the fact that each of the bacterial species tested had significantly different effects on the mucosal gene expression profile (GEP) of each volunteer.  By this, I simply mean the following:

  • L. acidophilus elicited changes in genes involved in stimulating and regulating immune response (both innate and acquired: increased interferon and antibodies), and hormonal regulation of water and ion homeostasis, increased tissue growth and wound healing, and metabolism regulation.
  • L. casei lead to gene expression regulating the balance between innate and acquired immune response, as well as metabolism regulation and regulation of hormones involved in blood pressure.
  • L. rhamnosus caused expression of genes involved in wound repair and healing, innate immune response (interferon), and ion homeostasis.

All three bacteria stimulated responses involved in innate immune response, while L. casei also caused modulation (balance) of the innate vs. acquired immune response.  The authors noted that the response to each species of bacteria was markedly different, and that these differences could extend as far as the growth stage of the bacteria in the probiotics preparation.  What this means is that every probiotics product on the shelf is not created equal; the species, even variety, is important, and the methods used to cultivate and preserve the organisms may be important as well (i.e. live cultures are best).

Because of the fact that the technology used in the approach for this study is fairly new, we actually don’t have a lot of human mucosal gene transcription profiles to compare these types of data against (in other words, we can’t see how these data align with other data from similar studies, because there are not yet any other similar studies).  So, my first thought was something along the lines of, “How do we know the same GEP might not be elicited if somebody ate food, or anything for that matter?”   The authors expected questions like that and therefore compared their data with data from GEPs of human cell lines exposed to various compounds.  The results of this comparison were quite interesting:

  • L. acidophilus had similar effects to drugs for hypertension, convulsions, and inflammation.
  • L. casei caused had similar effects to drugs used to treat muscle hypertension, water retention, and inflammation.
  • L. rhamnosus elicited effects similar to drugs used against protozoan infections and to amplify bowel movements.

So, not only could they directly measure certain genes in the human stomach mucosa responding to the probiotics in a way that suggested modulation of the immune system (amongst other things) but the response was actually similar to the effects of drugs engineered to treat and modulate that very thing.  Fascinating! 

This study is obviously not the end-all and be-all of probiotics work, but it’s a huge piece of the puzzle in terms of why probiotic clinical trials have yielded such conflicting results, and particularly how probiotics modulate the immune system in a variety of ways and against a variety of afflictions.  It certainly supports the mouse-flu study I blogged a few weeks ago.  The authors conclude,

 “We anticipate that responsiveness to probiotics is not only determined by characteristics of the consumed bacterial strain but also by genetic background, resident microbiota, diet, and lifestyle.  This study could, therefore, be among the first steps to investigate the interplay between microbiota, probiotics, or other nutritional supplements and human genetics tow personalized nutrition.”

To me, this says that if you already have a healthy immune system, you work-out and eat right, get enough rest and all that, you might or might not notice a difference from taking a probiotic.  However, if you’re immune system is already compromised, you regularly drink, smoke, are largely sedentary, and stay up all night doing who-knows-what… if you opt for a cup of yogurt instead of a Twinkie, you just might thank yourself in the morning (and now we have the data to prove it!).

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ResearchBlogging.org
van Baarlen P, Troost F, van der Meer C, Hooiveld G, Boekschoten M, Brummer RJ, & Kleerebezem M (2010). Microbes and Health Sackler Colloquium: Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proceedings of the National Academy of Sciences of the United States of America PMID: 20823239

Shall we dance?…

29 Sep

This post was chosen as an Editor's Selection for ResearchBlogging.org… says the rhizobial bacteria to the leguminous plant root.  In response, the plant warmly embraces her partner, literally wrapping herself fully around the bacteria, and so the intricate and highly choreographed ballet begins.

Image of a root hair embracing it's bacterial consort, by Euan James, via Life Sciences at the University of Dundee.

But how can a minuscule little bacterium communicate to a “higher plant” in a way to elicit such an overwhelming positive response?  A response which catalyzes this fundamental and truly amazing partnership, on which the world as we know it has depended for millenia?

The answer is simple, these bacteria developed special signaling molecules called nodulation (Nod) factors to communicate with certain plants.  These nodulation factors are diffusible signals, which mimic plant hormones, and stimulate very specific developmental processes within the plant during the initiation of the symbiotic relationship (Oldroyd & Downie, 2008).  They provide the choreography of the dance.

By simply altering the length and degree of saturation (think, saturated vs. unsaturated fats) of the nodulation factors, bacteria can target very specific plants.  This species-specific tuning of the nodulation signals allows an individual bacterium to “speak to” the host it prefers and form a relationship with, for example, a soybean plant rather than an alfalfa plant.

Once the plant recognizes the nodulation factor of the rhizobial bacteria, infection occurs through root hair cells which curl around and entrap the attached bacteria.  The bacteria, in turn, begin to break down the plant cell walls which entrap them, and subsequently initiate the formation of a tube-like structure called the intracellular infection thread or IIT (Ivanov, et al. 2010).

Intracellular infection threads containing fluroescently labeled rhizobial bacteria.  (By Dan Gage)

Intracellular infection threads (IIT) containing fluroescently labeled rhizobial bacteria. (By Dan Gage)

The IIT serves as a biological inoculation needle, so to speak, penetrating the root primordial cells and releasing bacteria into the cytoplasm of the plant.  At this point, the plant cells form a protective membrane around the mass of bacterial cells, where the bacteria differentiate into their nitrogen-fixing stage.  This special intercellular plant membrane, also called the peribacteroid membrane (PBM), allows nutrient exchange and helps protect the bacteria from oxygen, which would destroy the nitrogenase enzyme crucial to the process of gaseous N2 fixation (the process which is central to the nitrogen cycle, controls nitrogen availability, and consequently supports life on this earth).

At every point in this intricate dance, the bacteria and plant are engaged in a complex dialogue; this constant communication prevents activation of the plant defensive systems and the final formation of a functional symbiotic relationship (i.e. an active root nodule).  It’s a beautiful and fascinating process on which we rely, and should duly appreciate.

So, when, in my previous post, I mentioned the fact that it perturbs me when people dismiss the role bacteria play in symbiotic nitrogen fixation, I hope you can see that saying “plants fix nitrogen” for me, is comparable to saying Da Vinci’s paintbrush was responsible for the Mona Lisa, or that Einstein’s pen introduced the Theory of Relativity.  It just doesn’t give credit where credit is due.

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ResearchBlogging.orgIvanov, S., Fedorova, E., & Bisseling, T. (2010). Intracellular plant microbe associations: secretory pathways and the formation of perimicrobial compartments. Current Opinion in Plant Biology, 13 (4), 372-377 DOI: 10.1016/j.pbi.2010.04.005

Oldroyd, G., & Downie, J. (2008). Coordinating Nodule Morphogenesis with Rhizobial Infection in Legumes. Annual Review of Plant Biology, 59 (1), 519-546 DOI: 10.1146/annurev.arplant.59.032607.092839