Microbiology

A spoon that’s spent some time in a functioning garbage disposal is not a pretty thing to see. But did you see what happened to the garbage disposal?

Stanford microbiologist pathologist Matt Bogyo, PhD, has had his own blades whirring for quite some time in a search for drugs to combat the organism responsible for malaria. This one-celled organism, Plasmodium falciparum, wells in the bodies of more than a billion people, hits 250 million new human targets every year (virtually all of them in developing tropical countries) and kills almost a million (most of them children). And the drugs that have, for years, worked effectively to stall the disease (in those victims fortunate enough to gain access to them) have started to stop working.

That’s where the garbage disposals come in. Virtually every living cell, from the ones that singlehandedly compose P. falciparum to the ones in the human body that the parasite is infecting, produce a lot of garbage. So, evolution being more than just another pretty face, all of these cells have in-house garbage disposals called proteasomes. These nano-appliances play a mega role in the everyday life of a cell whether it’s sick or healthy. As I wrote last August in a release about a very different topic:

[v]irtually all cells in creatures ranging from yeast to humans contain multitudes of these tiny tube-shaped machines, which suck… defective proteins into their holes and chop them into smithereens.

Suffice it to say that if you’re a protein you don’t want to fall into one.

All proteasomes – from those in the malaria parasite to those in our bodies – are pretty similar. But they have their differences. Bogyo and his teammates seem to have found a very discriminating molecular spoon: a derivative of a (conveniently) already-on-the-market cancer drug, carfilzomib, that just happens to gum up P. falciparum‘s garbage disposal, but not ours. The experiments leading to this spoon (a drug, actually) are described in this just-out study in Cell Chemistry & Biology.

Vive la difference!

Previously: Nervous breakdown: Preventing demolition of faulty proteins counters neurodegeneration in lab mice, Taming of the malaria parasite? Study takes us one step closer to vaccine and Malaria protection in wearable form
Photo by SanFranAnnie

In this amazing video, Tom Kirchhausen, PhD, a Harvard Medical School professor of cell biology, shows how tiny protein-bubbles form to carry cargo, such as nutrients and hormones, across cell membranes. Using Total Internal Reflection Fluorescence microscopy (TIRF), researchers were able to capture, for the first time, real-time footage of how this crucial cellular mechanism happens, providing new insights on how drugs might interact with life’s moving parts at the molecular level.

These findings were published in the August 3 issue of Cell.

As we’ve reported previously on Scope, cutting-edge techniques and cost-effective methods of rapidly sequencing entire genomes of bacteria and viruses are helping researchers better understand how the microbial communities in and on our bodies influence health.

But bacteria and viruses may not be the only microbes that shape our well-being. New research published in Science offers additional insight into how internal fungi have an impact on health. The findings (subscription required) show a signaling molecule involved in antifungal immunity could contribute to irritable bowel syndrome.

A post today on Wired Science offers a closer look at the study and the role fungi may play in our personal health. Brandon Keim writes:

Fungi are the latest addition to human menagerie, joining bacteria and viruses in forming the teeming, biological kingdom-spanning superorganisms of our bodies.

“We were all fascinated with the diversity and sheer mass of microorganisms that live inside our intestines,” said immunobiologist David Underhill of the Cedars-Sinai Medical Center. “So we started asking: What do we know about fungus in the gut?”

In a June 8 Science study, researchers led by Underhill and postdoctoral student Ilian Iliev link gut fungus to colitis, an inflammatory bowel disease.

While the findings may be presently useful to colitis researchers, the implications are sweeping: Scientists might ask the same questions of internal fungi as they do internal bacteria, the importance of which is now a buzzing research frontier.

The full story is worth taking a moment to read.

Previously: Cultivating the human microbiome, Contemplating how our human microbiome influences personal health and The dawn of a new era in microbiology

In a sense, our body is not our own. Microbes living in and around us outnumber our own human cells ten to one. A review in a special issue of Science leverages ecological theory to explore these most intimate relationships.

The authors, led by Stanford’s David Relman, MD, examine scientists’ understanding of how our microbial communities vary over time. They compare a newborn to communities moving into a newly created habitat (in ecology the common example is a new island), a human after antibiotic treatment to a disturbed habitat (a forest after a fire) and a person infected by a pathogen to a habitat under invasion from a foreign species.

This is not the first time experts have argued the microbes in our body follow patterns observed in larger ecosystems. That thinking has also led to a call for epidemiologists to learn ecology as a way to consider the microorganisms that live inside us.

The paper concludes with a challenge to the traditional perspective of the human body as “a battleground on which physicians attack pathogens with increasing force, occasionally having to resort to a scorched-earth approach to rid a body of disease.” Instead, the authors suggest clinicians could cultivate the human microbiome like park managers, encouraging conditions that favor good microbes instead of bad. By measuring biomarkers constantly, doctors could track the progress of disease and treatment. “Such an information-intensive approach, guided by ecological theory, has the potential to revolutionize the treatment of disease,” they write.

Previously: Contemplating how our human microbiome influences personal health and New York Times explores our amazing microbes
Photo by Eek

As previously reported on Scope, researchers at Stanford and elsewhere are engaged in ongoing efforts to determine how microscopic ecosystems that exist in the human body may impact personal health. Today, an opinion piece on Scientific American’s Observations blog examines how our evolving understanding of this microbiome community influence the “nature vs. nurture” debate.

Christine Gorman writes:

The latest research into the genetics of the human microbiome is taking to a whole new level the old (and not always fruitful) argument about whether nature or nurture is a more important influence in our lives.

…

The point is that the microbes that live inside, on and around us all ultimately come from the environment. And these commensal bacteria shape our lives every bit as much as our genetic inheritance does. In fact, in many cases, the genes found in these microbes allow us to do something—like digest the fiber in oranges—that our own genes cannot.

The old dichotomy of nature vs. nurture is meaningless when what we think of as our nature—namely the genes that make us who we are—can come from our parents or our microbes.

Previously: Study shows intestinal microbes may fall into three distinct categories, Your own unique microbial cachet?, Your bacterial birthday suit reveals the mode of your birth, Study links bacteria in gut to size of a “gut” and The future of probiotics
Photo by Wellcome Images

This brief video from Cambridge University’s Under the Microscope series shows a killer T cell, which measure 10 microns in length, identifying and attacking a cancer cell. The microscopic footage was captured by Alex Ritter, a PhD student in the lab of Gillian Griffiths, PhD.

Griffiths writes on the university’s YouTube page:

Cells of the immune system protect the body against pathogens. If cells in our bodies are infected by viruses, or become cancerous, then killer cells of the immune system identify and destroy the affected cells. Cytotoxic T cells are very precise and efficient killers. They are able to destroy infected or cancerous cells, without destroying healthy cells surrounding them … By understanding how this works, we can develop ways to control killer cells. This will allow us to find ways to improve cancer therapies, and ameliorate autoimmune diseases caused when killer cells run amok and attack healthy cells in our bodies.

Via The Atlantic
Previously: Tiny wonders: Small World in Motion competition winners bring microscopic activity to life

David Schneider, PhD, has used used two kinds of bugs (fruit flies and bacteria) to great effect, teasing out intriguing insights into the effects of sleep and caloric  intake on response to infection.

Much has been written about the power of the immune system to stave off infectious disease; not so much about the damage the immune response itself can inflict on the organism it’s designed to stave. If you’ve ever ever had influenza, you’re well aware of how rotten it made you feel. That was largely a byproduct of your immune response, which, in its zeal to destroy microbial pathogens, often attacks not only infected but healthy tissue. It also raises your body temperature to uncomfortable heights and squirts out inflammatory molecules and oxidants that, while nipping the bug in the bud, may weaken innocent nearby cells and render them more vulnerable to maladies later on.

A delicate balance must be achieved between destroying the invader and sparing the host. To the rescue comes another, less-talked-about aspect of disease control Schneider calls “tolerance” – not to be confused with “immunological tolerance,” the willingness of the immune system not to respond with a vengeance to every damned molecule it meets along the way.

For example, an animal may amp up production of anti-oxidant molecules to scavenge free radicals that are released by immune activity in response to an infection. Or, beset by the parasite that causes malaria, it might boost its output of a special molecule that mops up hemoglobin, which, when released from ruptured red blood cells into the circulation, can severely damage tissues.

In a just-out review article in Science, Schneider and two co-authors emphasize the importance of tolerance, a collection of mechanisms that increase an animal’s ability to withstand infection independently of its ability to clear the pathogen itself. They write:

The concept of tolerance may… be applicable to the “Typhoid Mary” phenomenon. Healthy carriers that remain asymptomatic despite being infected are likely to have a high level of tolerance to the pathogen with which they are infected.

As above, so below. In the world of one-celled invaders and, unfortunately, in the larger world we inhabit, we sometimes have to fight back even at the cost of considerable damage to the home front. And, in both these worlds, it seems, victory results from a mix of fighting and enduring.

Previously: Fruit flies fly while scalped, exposing their brain cells for science

Add this to your list of reasons to kick your cigarette habit: Recent research shows smoking may cause the body to turn against helpful bacteria leaving people who smoke more vulnerable to disease.

In the small study (subscription required), Ohio State University researchers took samples of oral biofilm from health non-smokers and healthy smokers one, two, four and seven days after receiving a professional cleaning. By analyzing DNA signatures found in dental plaque, researchers determined which bacteria were present and then monitored whether participant’s bodies were treating the microbes as a threat. According to a university release:

The team found that for nonsmokers, bacterial communities regain a similar balance of species to the communities that were scraped away during cleaning. Disease-associated bacteria are largely absent, and low levels of cytokines show that the body is not treating the helpful biofilms as a threat.

“By contrast,” said [Ohio State researcher Purnima Kumar, PhD,] “smokers start getting colonized by pathogens – bacteria that we know are harmful – within 24 hours. It takes longer for smokers to form a stable microbial community, and when they do, it’s a pathogen-rich community.”

Smokers also have higher levels of cytokines, indicating that the body is mounting defenses against infection. Clinically, this immune response takes the form of red, swollen gums – called gingivitis – that can lead to the irreversible bone loss of periodontitis.

In smokers, however, the body is not just trying to fight off harmful bacteria. The types of cytokines in smokers’ gum swabs showed the researchers that smokers’ bodies were treating even healthy bacteria as threatening.

Researchers say the findings could shape dental care practices for patients who smoke and motivate dentists to play a more active role in helping patients get the necessary support to kick their nicotine habit.

Previously: National Cancer Institute introduces free text message cessation service for teens, Kicking the smoking habit for good, How have U.S. tobacco regulations affected smokers?, Lung cancer rates declining in the U.S. and Study shows anti-tobacco programs targeting adults also curb teen smoking
Photo by LawPrieR

Yesterday, Nikon Instruments announced the winners of its inaugural Small World in Motion Photomicrography Competition. From a selection of more than 200 submissions, judges deemed 13 stunning videos to be the most visually outstanding as well as high-caliber depictions of the intersection of science and art.

This time-lapse movie showing the movement of mitochondria in sensory neurons in the tail of a zebra fish larva took second place. MSNBC reports:

Mitochondria are the energy-producing powerhouses of the cell, and play a vital role in sparking neural activity. This movie was created in the course of [postdoctoral fellow Dominik Paquet's] research into the molecular and cellular pathologies associated with dementia and Alzheimer’s disease.

Paquet and his team at the German Center for Neurodegenerative Disease in Munich were studying how problems with the transport of cellular components can affect nerve cells. Paquet says this video may represent the first-ever example of live imaging of mitochondrial transport in the nerve cells of an intact, unmodified vertebrate.

Paquet discusses additional details about the video in this brief Q&A. Additional winning videos can be viewed here.

Previously: Wired Science picks 16 interesting science visualizations and Video: “Seven Wonders of the Microbe World”

This neat little documentary from Open University catalogs seven “wonders” of the microbe world, from the making of beer to what caused the Black Death pandemic and what happened as its result (perhaps, they say, the English Reformation). It’s well produced, interesting and worth watching.

Via The Atlantic