Small Things Considered

Microbes or Not, Parasites All

by Elio

The adult protozoon, Spirochona gemmipara, on the gills of a crustacean. Source.

Parasites pose a problem for the semantically-oriented microbiologist. There is no question that unicellular parasites such as Giardia, Plasmodium, or Toxoplasma are microbes, thus we can appropriate them with impunity. But what about parasitic worms? They are clearly not microscopic* and are taxonomically apart from parasitic protist. Yet parasitic protists and metazoans are taught alongside one another in the microbiology classroom and they are often considered in unison by epidemiologists and others. For all their phylogenetic divide and apparent differences, they all share the general traits of a parasitic life style, including undergoing the same steps in pathogenesis (encounter with the host, entry, survival, multiplication, causing damage) and eliciting complex immune responses.

A nematode, Strelkovimermis spiculatus, parasitizing a mosquito larva. Source.

Particularly fascinating is that parasites have evolved intricate mechanisms to survive inside the host and ensure their transmission. Many parasites, whether unicellular or multicellular, go through life cycles that are ultra-baroque in complexity. Consider, for example, the malaria plasmodia’s contortions both within the mosquitoes and the humans. Plasmodia interact with at least three kinds of cells in the insect host and go through some six different stages of differentiation in the human host (including sex). Or ponder about certain flukes that go through as many as four distinct hosts in their life cycle! 

So, somewhere along the line, us microbiologists should consider nuzzling up to the metazoan parasites, at least to learn more about them. The Internet is a good place to start, with a number of fine blogs, articles, and other forms of social media that are both informative and exciting. Visiting them is more than just worthwhile. Here is a partial list:

This Week in Parasitism is an ASM-sponsored podcast hosted by Vincent Racaniello and Dickson Despommier where a wide range of issues of parasitism are artfully discussed.

Parasite of the Day presents a parade of unusual and unexpected parasites, from some that are found in tar pits to others that feed on mosquito larvae.

Pretty Protozoa deals with unicellular parasite species in ways that satisfy both the eye and the mind.

10 Astonishing Examples of Bizarre Parasitic Life Cycles presents a small parade of parasites, from those that make their crab host dance, to one that eat the fish host’s tongue, to those that make their fly host dive in a lake.

The Artful Amoeba has exquisitely written articles, occasionally on parasitic forms.

*A human tapeworm can reach 10 meters in length, that of a whale, 40 meters.

Let’s Start Out Big

by Elio

A Xenophyophore from the Galapagos Rift observed from the US National Oceanic and Atmospheric Administration's Ocean Explorer. Photograph by NOAA. Source.

We are embarking on our seventh year, not a bad age for a blog, and we continue to be astounded by the fanciful tales from the pint-sized world of the Small Things. So, just to be contrary, I’ll start out with a story of a group of giants among microbes, the single-celled protists called Xenophyophores.

If you were to visit the deep-sea bottom in many parts of the world, you would see a lot of these organisms. You couldn’t miss them, being that some are the size of a regular pancake. Had you been aboard the recent James Cameron Deepsea Challenger expedition to the deepest part of the oceans, the Mariana Trench in the western Pacific, you would have found them even there. Never heard of them? You’re not alone, as neither had I. This is something we should remedy, being that the Xenophyophores may be, depending on your criterion, the largest single cells extant—some  reaching 20 cm in diameter. It’s no wonder that in 1889 their discoverers first thought they were sponges. But single cells they are, endowed with many well-spaced large nuclei, each 2-10 μm in diameter.

Fine Reading: Houses Made by Protists

by Elio

Euglypha rotunda test showing some 120 extremely
regular, overlapping tiles that, prior to cell division,
become arranged around the newly budding organism.
A further 8 to 14 slightly thicker, toothed tiles
surround the aperture. Source.

If there is a limit to what unicellular organisms can do, you can't prove it by me. As Michael Hansell writes in an article entitled Houses Made by Protists, some single cells can make exceedingly intricate structures. Using a Q&A format, Hansell, who bears the interesting title of Professor of Animal Architecture at the University of Glasgow, discusses examples that defy the imagination.

Take for instance the pyramids of Egypt. They are made of huge limestone blocks of fossil shells of ancient foraminifera (forams). These are true giants among the protists, making shells that reach 10 cm across. That’s some amoeba! (The ancient Greeks thought they were petrified lentils. That’s some lentils!) A lovely account of this gigantism can be seen in a site called Pyramids, forams, and Red Sea reefs: Field notes from Lorraine Casazza. Foraminifera are not the only ones to make houses; the so-called testate amoebas do, too. (“Testate” refers to tests, the name of such shells. A confusing term, that. Try giving a test about protist tests.)

Fine Reading: Two Fine Protist Blogs

by Elio

Merry and I would like you to know about two specialized blogs that deal mainly with protists, one called Skeptic Wonder, the other The Ocelloid. The first one is a spirited blog whose history goes back to 2008, the second a recent addition to the Scientific American Blog Network. Both are written by a friend and avid protistologist who goes by the name of Psi Wavefunction, and we’re glad to help publicize them.

We applaud the blogger's effort, in good part because we believe that protists need good press. Everyone has heard of them, perhaps encountering them as pond-scum paramecia in high school, when learning about malaria, or more recently in the hoopla about using micro-algae to produce fuels. But they deserve more attention than that for their enormous variety in shape, size, and genomic complexity. They have a central role in this planet’s metabolism, being responsible for a huge amount of carbon cycling. In addition, many, like the diatoms, are a joy to the eye.

The first issue of The Ocelloid is A Quick Dive into the Protist World, and quite a trip it is. Here you'll encounter organisms you may have heard about, or not—intricate radiolaria, filose amoebas that leave tracks on the sand, and gorgeous foraminifera. The name of this blog refers to an eye-like structures of dinoflagellates, the ocelloid. This is a true model biological wonder, with a complexity that approaches that of the vertebrate eye, all in one unicellular organism.

Many blogs deserve your attention, but these two stand out in our opinion.

 

Hard Biology

Pleurosigma (a marine diatom). Credit: Michael
Stringer, Westcliff-on-Sea, Essex, UK. Source.

by Elio

For some time, I've had the urge to learn something about diatoms. They are dazzlingly beautiful, relatively easy to manipulate, and have left a fossil record immense in quantity. I never had followed up on this yen, so here’s my chance. A recent paper shed light on the way they make their hard shells.

Diatoms are busy creatures, accounting by their photosynthesis for about 20% of the global primary production of organic material, an amount comparable to that produced by the tropical rain forests. They are single cells contained within a shell made up of glass (silica), which is what gives many of them often stunning shapes. Silica does not readily decompose and fossil diatom shells accumulate in prodigious quantities. Such deposits can be hundreds of meters deep in some places (fossils by the truckload!). Diatomaceous earth, as the rock consisting of fossil diatoms is called, has a large number of industrial uses, such as filtering pool water, absorbing oil spills, as a mechanical insecticide, as a mild abrasive (it may well be in your toothpaste!), and even as a component of dynamite! And, as we will see below, diatoms also have novel and unexpected uses.

Targeting an Achilles' Heel of Plasmodium

by S. Marvin Friedman

SEM of female Anopheles mosquito. Source.

Plasmodium falciparum accounts for 85% of all cases of malaria, and thus is the most deadly of the many species in this genus. About 250 million people are infected annually, of which about one million die. Of these deaths, 90% occur south of the Sahara desert in Africa, and most of the victims are children under the age of five. Malaria also occurs in southern Asia, Central and South America, the Caribbean, and the Middle East. Plasmodium, an apicomplexan protozoan, is also famous for its complex life cycle, some stages of which take place while within females of certain species of Anopheles mosquitoes, others while resident in the liver and red blood cells of humans who were bitten by these mosquitoes. The huge health problem of malaria is exacerbated by the alarming ability of this protozoan to rapidly develop resistance to chemotherapeutic agents. Thus, new antimalarials are desperately needed to bring this deadly disease under control.

In order to identify new drug targets, Istvan and coworkers analyzed P. falciparum mutants resistant to two commonly used antimalarials: thioisoleucine (an analog of isoleucine) and mupirocin (an antibacterial agent used clinically to treat MRSA infections). These two drugs kill blood stage parasites at micromolar and mid-nanomolar concentrations, respectively. For both drugs, increasing the isoleucine concentration in the medium increases the IC50 values (i.e., reduces killing efficiency), suggesting a competitive interaction between isoleucine and both drugs. The kinetics of killing are dissimilar for these two compounds, indicating that they inhibit different isoleucine utilization targets. These results are not surprising since, upon entering red blood cells (“ring stage”), the parasites degrade hemoglobin to obtain a supply of amino acids necessary for replication. Such scavenging is essential because the parasites lack most amino acid biosynthetic pathways. But isoleucine is the only amino acid absent from adult human hemoglobin, hence is the only one that must be obtained from other, less convenient sources.

Farmer Joe Dictyostelium

by Elio

A scanning electron micrograph showing the various stages of
transformation of Dictyostelium. Each body represents a different
stage in the process. Hundreds of thousands of single cells
aggregate to form a migrating “slug” (lower left). Once the slug
comes to a stop, it gradually elongates to form the fruiting body.
[Courtesy of M. J. Grimsom & R. L. Blanton, Texas Tech Univer-
sity]. Source.

The practice of agriculture is not limited to humans: ants, termites, and snails all grow fungi, and who knows who else do something similar. But not many have claimed that such activities are to be found among simpler organisms. Now we have a report that slime molds have also gone down the road to agriculture. Dictyostelium discoideum, the best studied of the cellular slime molds, is a social amoeba that thrives by grazing on bacteria. Given ample bacterial food, these organisms grow as single cells. When food becomes scarce, they aggregate into pretty, differentiated fruiting bodies (called sorus, plural sori) consisting of a round mass of spores held up by a stalk. The spores eventually become dispersed, to repeat the cycle at a new site. The entire epic can be viewed in a dramatic documentary available here. (This movie is narrated in German, giving you the opportunity to hone your skills in that language.)

Naegleria’s Split Morphology Disorder

by Psi Wavefunction

The complex structure of flagellates. EM section through
a mature flagellate Tetramitus. K1 = kinetosome. Cm =
cytostomal canal. FV = food vacuole. Rz = rhizoplast.
Source.

By default, a membrane-bound entity like a cell should be a spherical, formless blob. However, most cells are not such formless blobs, but rather have adopted one or more forms from a vast repertory of stunningly complex morphologies. To wit, see (and admire) the radiolarians, metazoan neurons, giant parabasalians or the endlessly weird and sophisticated ciliates. Even prokaryotes have a highly complex cellular structure, and are not, as some biochemists are prone to think, mere bags of enzymes. The deeper you venture into the realm of cellular diversity, the more awe-inspiring becomes the cornucopia of cellular structural and morphological variety. Luckily, there is some order to it as there are two fundamental 'genres' of cellular morphology, at least in the protists: flagellates and amoebae. Of course, there are also cysts, but since those are mostly resting stages (being a round ball isn't particularly helpful while feeding or fleeing from predators...) they can be ignored for now.

Cell shape depends on the cytoskeleton. As you know, its two main component systems are actin and tubulin, ignoring the plethora of miscellaneous proteins that are used for various structural jobs. Tubulin makes microtubules, the spindle fibers of mitosis, but is also important for the flagellar apparatus (we've yet to find one composed of actin and probably for good reasons). You also know that actin is a key player in cell motility and morphology in animal systems. It is also heavily involved in endomembrane trafficking within a cell, as well as endo- and exocytosis. If interested, a recent issue of Science has a nice overview of actin in morphogenesis and cell movement.

The role of the cytoskeleton in morphogenesis is much less clearly defined. It depends largely on the species. Plants, for example, rely very heavily on tubulin for morphology, with actin being a minor player. Amoeboid cells are primarily actin-based. In fact, amoeboid cells resort to tubulin largely for spindle formation during mitosis. They hate tubulin about as much as plants hate actin. Actin-based cells don't have to be amorphous; they are still able to achieve complex morphologies. But there is a positive correlation between amoeboid-ness and actin-ness ('actinity'?).

In contrast, flagellates are primarily tubulin-based. Of course, they still use actin for some intracellular work, but the shape depends largely on the whims of their microtubules. Perhaps not relying much on flagella allows the amoeboids to dispense with the microtubule organization pathways, thereby switching to actin. Flagellates, relying heavily on intact tubulin systems, may be less prone to losing their structure. Also, if you're a flagellate, you need shape for a modicum of streamlining. Try swimming around as a formless or floppy blob of some sort! Keep in mind that life at that scale is very different. Viscosity calls the shots when considering unicellular motility. Perhaps being hydrodynamic isn't even as important as simply retaining shape. Otherwise you'd be like a blob of molasses trying to swim through a sea of maple syrup. Not gonna get very far.

Whatever the reason, amoeboid cells tend to have a predominantly actin-based cytoskeleton, flagellates have a penchant for tubulin. Of course, not all organisms are decisive enough to make this commitment, so we've got amoeboflagellates in the middle.

Plenty of other organisms fancy transitioning between being more amoeboid or more flagellate. But few cells actually dispense with flagella and basal bodies altogether, to form them anew when special conditions arise. It's time to introduce one that does.

Genomic Secrets of P. infestans, the Master of Potato Blight

This is the third and final post for our week of the oomycetes. In our first post, Elio provided the foundation by answering five key questions about this often neglected and misunderstood group. This was followed by a reminder from Mercè Piqueras of the role one member, the potato blight pathogen, has played in our history. Here in this final offering, Merry explores what we now—more than 150 years after The Great Famine—know about this pathogen's tactics from its genome sequence.

by Merry

No fungicide has ever been found to which P. infestans could not ultimately adjust…Indeed, no potato has ever been developed with defenses that Phytophthora could not ultimately breach. (Glenn Garelik. Source)

More than 150 years after the historic Irish potato famine, the deadly pathogen responsible for potato blight, Phytophthora infestans, is now destroying more than $3 billion worth of potatoes each year. What is the secret of it's pathogenic success? Hoping to find some answers in its genome, a team of 96 researchers have sequenced virtually its entire 240 Mb genome. This is by far the largest and most complex genome sequenced among the chromalveolates, a diverse eukaryote supergroup that includes not only the stramenopiles (the oomycetes, diatoms, and some algae) but also the dinoflagellates and the apicomplexans.

Why so much DNA? That's more than double that of Caenorhabditis elegans.

A Mold That Changed the Course of History

In this, the second of our three posts focusing on the oomycetes, we are pleased to offer a post from the blog by Mercè Piqueras, La lectora corrent (The Common Reader), translated here from Catalan.

by Mercè Piqueras

Micrograph of an oospore of Phytophthora
infestans. Source.

Recently, Nature published an article about the genome sequence and analysis of Phytophthora infestans, the oomycete that caused the potato blight in the nineteenth century that changed the course of history. Phytophthora infestans is the reason that today about 11% of the population of the United States is of Irish origin and that the population of Ireland was lower at the end of the 20th century than it had been in the first half of the 19th century.

Symptoms of potato late blight on potato
leaves. Source.

People who migrated to the United States in the 19th century did so for the same reason that pushes many people to migrate today to Europe from Latin American or African countries: to improve their living conditions, sometimes simply to survive. Hunger to the point of starvation was the main cause that pushed many Irish to go to the United States. That hunger even has a name of its own: The Great Famine in English and Am Gorta Mór in gaèlic The cause was potato blight, a pest that is still difficult to control today, although there are several ways to try to prevent it. Potatoes, originally from the Andean regions of South America, were introduced in England in the mid-16th century by Sir Walter Raleigh, who planted them in the fields of his estate in Ireland. In the 17th century the crop spread throughout the island, supplementing the Irish diet that had consisted mainly of cereals and dairy products. By the early 18th century, potatoes had become the staple food of the poor during the winter, and its culture became more and more widespread.