Do you know of any eukaryotic virus that has a tail, and, if not, why do you suppose there aren’t any?
Do you know of any eukaryotic virus that has a tail, and, if not, why do you suppose there aren’t any?
by Jamie Henzy
Figure 1. This comparison of skulls from a modern human (left) and Neanderthal (right), from the Cleveland Museum of Natural History, shows the larger cranial capacity of Neanderthals. Source.
From the discovery of the first Neanderthal skull in a Belgian cave in 1826, a bone of contention among Homo sapiens has been the extent of our relationship to Homo neanderthalis, who disappeared from the fossil record ~30,000 years ago. Like scrappy cousins we'd rather not claim, we've attempted to distance ourselves and establish our clear superiority, leading at times to suspect interpretations of data. For example, Neanderthal cranial capacity was larger than ours by about 25% (1500-1800 cc, compared to 1300-1500 cc for modern humans). To an unbiased observer, this feature could imply greater intelligence among Neanderthals. However, we have often chosen to depict Neanderthals as grunting brutes whose large heads evolved to allow frequent head-butting, as well as protection from blows from each others' clubs. But history is written by the winners, and as long as bones couldn't talk, we were free to impose upon them our preferred narrative.
Figure 2. The subpopulation of humans that left Africa for parts of Europe and Asia encountered Neanderthals and interbred with them, resulting in Neanderthal genetic sequences in modern non-African populations. Source.
Neanderthals Meet the Genomic Era
These days, however, the Genomics Age has given voice to the Stone Age, as Neanderthal DNA from 38,000 to 45,000 years ago has been successfully extracted from teeth and bone marrow, sequenced, and assembled, providing a map of the Neanderthal genome. Several findings require adjustments to the grunting brute narrative. First of all, Neanderthals share with humans the exact variant of a gene, FOXP2, that when absent in humans results in an inability to speak and process language. This allele is not found in chimps and gorillas—our closest living relatives—and along with archeological evidence of symbolic behavior, strongly suggests that they used language. Moreover, materials extracted from Neanderthal teeth indicate that they ate cooked vegetables. And the notion that ancient humans and Neanderthals represented separate species was dealt a blow when it was discovered that 1-4% of the genomic sequence of modern Europeans and Asians was contributed by Neanderthals, strongly suggesting that Neanderthals and the ancestors of modern humans interbred and produced fertile offspring. No separate species, they. In fact, some of the gene variants contributed by Neanderthals are thought to have aided the immune system of early humans.
Vincent, Michael, and Michele explain how the gut microbiome modulates colon tumorigenesis, and regulation of intestinal macrophage function by the microbial metabolite butyrate.
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Two people who mattered to me and to many other people have died recently. I wish to honor their memory by sharing a glimpse of them with you.
Manny died on January 8, 2014, one month shy of his 96th birthday. A member of a distinguished Swiss family, he earned his MD in Basel and soon thereafter went to New York City to work with the fabled Rene Dubos at the Rockefeller, training in immunological aspects of the tubercle bacillus. From there he moved to Harvard Medical School, and later he accepted the position as chair of the new microbiology department at the University of Florida Medical School. I joined this department shortly afterwards and was privileged to work under Manny for the next four years. Our department became quite distinguished in a short time, thanks to his innovative and hugely humanistic approach to teaching and administration. Following his instincts, he developed a series of distinctly Suterian ‘Instant Traditions’ that both taught and inspired. For instance, he had the medical school faculty gather in the cafeteria to discuss issues as wide-ranging as the philosophy behind testing and grading, along with questions as specific as: "Should a qualified applicant with a diagnosis of schizophrenia be admitted to medical school?" (His answer was yes.) He maintained that "People don't exist for institutions; institutions exist for people."
In his research, he inoculated innumerable mice with the attenuated tubercle bacillus BCG in order to probe into a phenomenon he had discovered, that mice infected with BCG become exquisitely sensitive to endotoxin (LPS). This work spearheaded efforts that led to an understanding of the complex interaction between macrophages, LPS, and what are now called cytokines. Despite leading a productive research program, he did not short-change the med students. In the late 50’s, research was so predominant in medical schools that teaching was becoming something of an afterthought (a sad fact that some maintain holds to this day). Not so there. Manny made us teach our butts off and like it. His tools were persuasion and occasional dry humor. For example: The then dean of the Medical School was particularly proud of our buildings and involved in its running (he called the elevators “vertical transportation”). He noted with distress that our hallway was ever so cluttered with refrigerators and incubators. He said, "Whenever I come up here, there is another piece of equipment in the hallway." To which Manny replied, "Then don't come up here!"
by Merry Youle
Figure 1. Source.
Gram-negative bacteria pose a particular challenge to any enterprising phage. First the phage is met by the outer membrane (OM)—a barrier to surmount that also can be used as a convenient handgrip for adsorption. Next hazard is the nuclease-infested periplasm with its jungle of peptidoglycan. An infecting phage genome needs protection to cross that compartment intact. For this, most tailed phages (the order Caudovirales) use the ‘long straw’ method. These phages are equipped with l-o-n-g tails for bridging the periplasmic moat. But what about the short-tailed ones such as T7? And what about the roly-poly icosahedral phages that have no tail at all? They all have one innovative solution or another. As evidence, here are three diverse examples of delicious phage ingenuity.
Figure 2. Schematic of a T7 virion before and after ejection of the internal core proteins to extend its tail. Together gene products 16 (gp16) and 17 (gp17) actively translocate approximately the first kbp of the T7 genome across the periplasm and into the cytoplasm. Source.
The mechanism used by the short-tailed phage T7 for crossing the host’s envelope layers is to extend the length of its tail upon infection. This tactic has been intensely studied and widely reported (see here and here). In brief, each T7 virion carries tail extension proteins as an internal core that is precisely positioned adjacent to the tail portal. This core is composed of three different proteins, in quantities of ten, eight, and four respectively. Upon adsorption, these proteins exit the capsid in a specific sequence ahead of the DNA to form a tube. This added-on conduit extends T7’s basic 23 nm long tail to 40-55 nm, long enough to easily bridge the periplasm and penetrate the cell membrane (CM). These ejected proteins do more than just extend the tail. As the tail extends, they help clear a path to the CM by digesting the obstructing peptidoglycan. During genome delivery they work in concert to ratchet approximately the first kbp of the genome into the cytoplasm, then put on the brakes. The rest of the genome is then pulled in by transcribing RNA polymerase. Its work finished, the tube disassembles, resealing the punctured cell membrane as it disappears.
by Fred Neidhardt
We reprint here portions of an article that first appeared in this blog in December, 2009.
Fig. 1. One of the first successful 2-d gels of the E. coli proteins, which is what made proteomics possible. Source.
By the mid-1970’s my mind, filled with unanswered questions about growth physiology, was searching for a new way to approach the bacterial cell. That way was revealed, not by anyone in my laboratory, but by a graduate student named Patrick O’Farrell at the University of Colorado at Boulder. A postdoctoral fellow in my laboratory at the University of Michigan, Steen Pedersen, one of the keenest of disciples of Ole Maaløe in Copenhagen (and one of his most honest critics) returned from a visit to Colorado in 1974 and reported to our laboratory that a graduate student there had produced a two-dimensional polyacrylamide gel system that could resolve the proteins of a bacterial cell on an array that looked as cool as “the sky on a starry night.”
Steen’s information electrified us, for we realized that a fundamentally new approach to bacterial growth physiology had become possible. Instead of asking the cell for information about a protein of interest to us, we could finally interrogate the cell about the proteins that were important to IT in any given situation. The cell could now reveal to us what lay behind the biological Green Door (in reference to an infamous American pornographic film of that era). For the first time the road to a global analysis of cell physiology could be imagined. And, in retrospect, it is clear that the era of proteomics began in 1975, the date of publication of Patrick O’Farrell’s thesis research in the Journal of Biological Chemistry. His paper was quickly recognized by a variety of molecular biologists as a true technological breakthrough. Citations in the next 30 years numbered over 16,000 (in spite of the fact that the manuscript was initially rejected with two disparaging reviews which had to be overruled eventually by members of the journal’s editorial board).
by Johnna L. Roose
Fig. 1. A Happy Couple. Source.
Do you ever look at a couple and wonder… ‘Why are they together? What does X see in Y. I just don’t get it. Is X in it only for the money’? Who doesn’t at times ponder about such matters? There’s practically an entire economy based on it. However, you didn’t find this article while waiting to check out in the grocery line. This post isn’t about celebrities; it’s about microbes. No matter—some microbe relationships have us scratching our heads and, to the same degree, casting premature judgment.
Fig. 2. Scanning electron micrographs of “Chlorochromatium aggregatum”. (A,B) Epibionts are shown in false color green, central bacteria in false color purple. (B) The central rod is dividing, and most of the epibiont cells have dissociated from the consortium. Scale bar in (B) equals 1 μm. Source.
Two Heads Beat One
One great example of such a conundrum is represented by the phototrophic consortium Chlorochromatium aggregatum, (this invalid name derives from an ancient era, when it was thought to be a single organism). In fact this is an unusually sophisticated prokaryotic symbiosis between a central motile heterotroph (Candidatus Symbiobacter mobilis) surrounded by multiple epibiont cells of a photoautotrophic green sulfur bacterium (Chlorobium chlorochromatii) (Figure 1). At first glance, this seems like a reasonable pairing, to combine mobility with photosynthetic autotrophy for the benefit of both organisms. Taking a deeper look at this relationship raises more questions. According to Don Bryant, "The relationship of these organisms is that of a highly dysfunctional marriage between a workaholic/nitrogen fixer/primary producer that is strictly anaerobic, and an oxygen-requiring, stressed-out, addicted soccer person that provides the bus, the driver and the GPS system.” Thus, in the microbial world as elsewhere, relationships are more complicated than they seem to be.
To gain insights as to how these organisms make this tryst work, researchers have, not surprisingly, turned to genomics for answers. In Genome Biology, Liu and co-authors report the complete genome sequences of both Chl. chlorochromatii and Ca. S. mobilis (Figure 2). They uncovered plenty of interesting details on the intimate relationship between these two organisms.
by Stanley Falkow
Fig. 1. Trouble jumping in? Source.
A graduate student came to my office recently to say that she was increasingly bothered by anxiety and the ‘terror’ of having to speak at laboratory meetings. She had also learned a month ago that she was expected to lecture to a class organized by her mentor. The thought of having to lecture to 20 or so complete strangers had now led to sleepless nights and she was physically ill as well as mentally distressed. She had been told that all of this could be ‘fixed’ by a small dose of a beta-blocker or an anti-anxiety drug like Ativan. She had tried this but it did not help her enough and she was now seeking my counsel because she had been told that I had written that I suffered from similar symptoms when I was a young scientist. Did I have a secret I could share? She confided in me that she was considering giving up her life long dream to become a ‘college professor’. I gave her several pieces of advice and told her how I was first able to get some relief after my first attempt to lecture to medical students in 1966. It occurs to me that this student may not be alone and I have heard from a number of people that reading my ‘confession’ that I had suffered from panic attacks early in my career had been helpful to them. So perhaps the readers of my favorite blog might find it helpful as well.
by Lucas Brouwers
Fig. 1. The Pink Lakes in Australia are coloured pink by salt-loving microbes. Photo by Neilsphotography. Source.
We're pleased to reprint here in slightly shorted form a recent post from Lucas’ Thoughtomics, a Scientific American blog whose aim is “Exploring evolution through genes, computers and history." By kind permission.
Microbiologists have long noted something odd about the Halobacteria (and not only their misleading name. They got it before the Archaea became known). In all their evolutionary analyses, they found that Halobacteria are part of a branch of archaea, the ‘methanogens’. What bothers microbiologists is that methanogens and Halobacteria couldn’t be more different. In every scheme ever devised to differentiate among microorganisms, methanogens and Halobacteria end up on opposing sides of the divide. If microbes were spices, methanogens would be the pepper to the halobacterial salt.
Methanogens are the self-reliant survivalists, able to liberate energy from the most basic of molecules. A pinch of hydrogen (H2), a dash of carbon dioxide (CO2) and a spoonful of minerals is all a methanogen needs to carve out a living. This sober lifestyle has earned them the moniker of ‘rock eaters’ (lithotrophs).
As is our custom, we take a two week vacation at this time of year, deserved or not. We'll see you again in the new year, starting on January 6th. Please accept our wishes for a fine Holiday Season. May cheerful thoughts of the Small Things dance in your head.
My thanks go to Andrea Gwartney who manages the technical aspects of this blog with rare skill and unmistakable dedication. I also thank Erika Shugart, Director of Communications and Strategic Marketing and Chris Condayan, Manager, Public Outreach, of the ASM staff who have fostered this cause with sensitive care and great perception. All have made the task much more pleasant.