Real-Time High Resolution 3D Imaging of the Lyme Disease Spirochete Adhering to and Escaping from the Vasculature of a Living Host. PLoS Pathog 2008 4(6): e1000090
Pathogenic spirochetes are bacteria that cause a number of emerging diseases worldwide, including Lyme disease. Spirochetes exhibit an unusual form of helical motility and can infect many different tissues. However, the mechanism by which they disseminate from the blood to target sites is unknown. Direct visualization of bacterial pathogens at the single cell level in living hosts is important, since this approach is likely to yield critical insight into disease processes. In a recent paper, researchers engineered a fluorescent strain of Borrelia burgdorferi, the Lyme disease pathogen, and used confocal microscopy to directly visualize these bacteria in real time and in 3D in living mice. They found that spirochete interaction with and dissemination out of the vasculature was a multi-stage process of unexpected complexity and that spirochete movement appeared to play an integral role in dissemination. This is the first report of high resolution 3D visualization of a bacterial pathogen in a living mammalian host, and provides the first direct insight into spirochete dissemination in vivo.
In the first section of this video you can see B. burgdorferi moving in the ear of a living mouse. The second section shows B. burgdorferi in a postcapillary venule in the skin of the mouse, and the third section shows the actual moment of escape from the blood vessel into the surrounding tissue.
On June 17 1867, the British surgeon Joseph Lister was the first person to perform surgery under antiseptic conditions. Lister came from a prosperous Quaker family in Essex and graduated with a degree in medicine from the University of London. In just a few years he became Professor of Surgery at the University of Glasgow. At that time the usual explanation for wound infections was that the exposed tissues were damaged by bad smells in the air which were called “miasma”. Hospital wards usually smelled bad, not due to “miasma” but due to the rotting of infected wounds.
Although anesthesia had been introduced in the preceding decades, post-surgical death rates ran at 40 to 50 percent because of hospital-acquired infections such as septicemia. Scientists were just beginning to make the connection between hygiene and infection. Hungarian physician Ignaz Semmelweis had discovered in 1847 that the simple act of obstetricians washing their hands in a chlorine solution could cut deaths from childbed fever from 10 percent to less than 2 percent. Lister had not heard of Semmelweis, but it is usually believed that his work to reduce mortality rates in British hospitals stemmed from his reading of Louis Pasteur’s research. In 1865, Pasteur reported that microorganisms cause matter to ferment and eventually rot. Lister made the connection between Pasteur’s research and his own profession.
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Carbolic acid (phenol) had been used by the authorities in the town of Carlisle to treat smelly sewage, so Lister tested the results of spraying instruments, surgical incisions and dressings with a solution phenol. He also found that phenol solution swabbed on wounds markedly reduced the incidence of gangrene and subsequently published a series of articles on this finding. He also made surgeons wear clean gloves and wash their hands before and after operations with 5% phenol solution. Instruments were also washed in the same solution and assistants sprayed the solution into the air in the operating theatre. Another of his innovations was to stop using porous natural materials in manufacturing the handles of surgical instruments.
Lister reported that his surgical wards remained free of sepsis for nine months. Between 1864 and 1866, Lister lost 46 percent of his surgical patients. From 1867 to 1870, he lost “only” 15 percent. By 1877, he had dropped the death rate to 5 percent. As the germ theory of disease became more widely accepted, it was realised that infection could be better avoided by preventing bacteria from getting into wounds in the first place. This led to the development of sterile surgery. Lister went on to pioneer new surgical techniques, became Baron Lister of Lyme Regis and was made one of the twelve original members of the Order of Merit. The bacterial genus Listeria, including the food-borne pathogen Listeria monocytogenes, was named in his honour.
The Baas-Becking hypothesis, also known as the “everything is everywhere” (EisE) hypothesis, encapsulates the classical view that microscopic organisms are globally distributed due to their high dispersal potential. Small size and an ability to enter dormancy might explain why prokaryotes and some microscopic eukaryotes, such as protists and small invertebrates, have acquired global distributions. The assumption that organisms smaller than 2 mm have a cosmopolitan distribution is often true when species are defined using traditional taxonomy. However, the EisE hypothesis has been challenged recently as molecular evidence revealed a high degree of cryptic diversity and restricted dispersal in a variety of microscopic organisms, including prokaryotes, protists and fungi. Other studies have found cases of restricted distributions by re-evaluating morphological evidence in species previously assumed to have cosmopolitan distributions.
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The current debate on the EisE hypothesis divides scientists in two major groups. On one side, scientists holding to the hypothesis in its original form assume that species differences in samples from different areas occur because of environmental differences, and not because of restricted dispersal. Thus, “everything is everywhere, but the environment selects” is considered the rule for microorganisms. On the other hand, other scientists propose that classical morphological taxonomy of microscopic organisms is not able to resolve their true diversity, and therefore that cosmopolitan ranges result from misidentification and lumping of spatially isolated lineages. So cosmopolitanism is considered as an exception in microorganisms, as it is in macroorganisms.
A recent paper tested the EisE hypothesis in an interesting test-case, the bdelloid rotifers (Molecular evidence for broad-scale distributions in bdelloid rotifers: everything is not everywhere but most things are very widespread. Molecular Ecology, 03 Jun 2008). Bdelloids are microscopic animals (the vast majority smaller than 1 mm) that have been regarded traditionally to have cosmopolitan species. The authors sampled living bdelloid rotifers from water in rivers, ponds and water bodies, and dormant animals in dry mosses and lichens. The sampling effort was greatest in Italy and the UK, with lesser sampling across seven other countries in Europe, including with 25 samples from Africa, Antarctica, Australia, New Zealand, North America and Southeast Asia. They used cytochrome oxidase I (COX1) sequence data to determine relationships. Many traditional bdelloid species were found commonly in almost every place sampled, supporting the idea of cosmopolitan distribution. Hence, the molecular data tended to support the traditional EisE hypothesis based on morphological species identification.
So what?
Rotifers are interesting organisms which have attracted some attention lately. As far as anyone can tell, the bdelloid rotifers are ancient asexuals - they appear to have been living entirely without sex for more than 85 million years (Who Needs Sex (or Males) Anyway? PLoS Biol 5(4): e99). Instead of reproducing via eggs and sperm, asexual organisms can reproduce in any number of ways. For instance, some bud off a piece of themselves; the piece grows into a whole new animal. The bdelloids, like many other asexuals, reproduce by means of eggs that don’t need to be fertilized. Evolving asexuality isn’t the hard part. The hard part is making an evolutionary success of this lifestyle. So rotifers steal genes. Bdelloid rotifers contain many genes that appear to have originated in bacteria, fungi, and plants. These fascinating organisms not only have relaxed the normal barriers to incorporating foreign genetic material, but more surprisingly, they even managed to keep some of these alien genes functional (Massive Horizontal Gene Transfer in Bdelloid Rotifers. Science 2008 320: 1210).
Nevertheless, although “everything is not everywhere”, bdelloid rotifers do display broad geographical distributions typical of those of other microscopic organisms. Broad dispersal and large population sizes might be factors lessening the evolutionary cost of long-term abstinence from sexual reproduction in this group of obligate parthenogens.
Dengue is a mosquito-borne disease caused by four serotypes of dengue virus (DENV1–DENV4) and is currently the most common arbovirus (arthropod-transmitted) disease worldwide. Primary infection with any of the four DV serotypes typically results in dengue fever (DF), a relatively mild influenza-like illness which subsequently provides lifelong immunity to the infecting strain. However, the bad news is that secondary infection with different DV serotype is associated with an increased risk of developing more serious conditions such as dengue haemorrhagic fever (DHF) and the life-threatening dengue shock syndrome (DSS).
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The first well documented outbreaks of dengue occurred in the eighteenth century, although the disease may have been around in China eight hundred years earlier. Dengue virus was first isolated by Japanese and American scientists during World War II. Dengue is now a major public health problem, with approximately 50 million people infected each year (of whom around 20,000 die) and nearly half the world’s population, about 3.5 billion people, at risk of infection. Unfortunately, no dengue virus-specific therapies or vaccines are currently available. The incidence of dengue infection has increased dramatically in the past 50 years. This is due in part to population growth and urbanization in tropical and subtropical countries. Originally found in the jungles and rural areas of Southeast Asia, dengue virus is now maintained primarily in an urban cycle involving human hosts and Aedes aegypti and A. albopictus mosquitoes. Urban areas frequently contain many breeding sites for the mosquitoes that transmit the virus, such as rain-filled old tyres. Successful mosquito control has also been problematic. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have expanded from South and Southeast Asia into the Pacific and the Americas.
The pathogenesis of dengue haemorrhagic fever and dengue shock syndrome remain unclear. The requirement for a second infection with a different serotype of the virus suggested that antibody-dependent enhancement is involved in these more serious conditions. After an initial period of protection, antibodies from the primary infection can cross-react with other dengue virus serotypes but have waned to non-neutralizing levels. These non-neutralizing antibodies could then mediate an increased uptake of virus into monocyte/macrophage cells via Fc receptors, leading to increased virus replication and immune activation including massive cytokine release (known as a “cytokine storm”). An alternative theory involves reactivation of cross-reactive memory T cells specific for the previous rather than the current virus strain, resulting in delayed virus clearance and/or increased cytokine secretion along with increased apoptosis of both infected and uninfected bystander cells (known as “original antigenic sin”).
With only around 65% homology based on amino acid sequence, the four dengue viruses could have been classified as separate virus groups but instead are treated as four serotypes belonging to a single group. It appears that there may be differences between the viruses, with DENV2 most commonly been associated with DHF/DSS and DENV4 the least likely to cause the more serious infections, but all serotypes can cause all of the conditions.
Because of the nature of dengue virus pathogenesis, a tetravalent vaccine effective against all four dengue virus serotypes is urgently needed. Vaccines which induce weak immune responses below protective levels over time are not acceptable because of the severe consequences of secondary DENV infections. Efforts to develop a dengue vaccine have encompassed live attenuated virus vaccines, inactivated virus vaccines, subunit vaccines and DNA vaccines. Vaccines of each type are currently or have been subjected to clinical trials, but none has yet been approved for use. Travelers to affected regions should take precautions against being bitten by mosquitos, use insect repellent day and night and check that hotels provide mosquito nets. Just another joy of those long-haul holidays.
Many but not all bacteria exhibit motility, i.e. self-propelled motion, under appropriate circumstances. Motion can be achieved by one of three mechanisms.
Most motile bacteria move by the use of flagella, rigid structures 20 nm in diameter and 15-20 µm long which protrude from the cell surface, e.g. the Chromatium cells in the video. In some bacteria, there is only a single flagellum - such cells are called monotrichous. In these circumstances, the flagellum is usually located at one end of the cell (polar). Some bacteria have a single flagellum at both ends - amphitrichous. However, many bacteria have numerous flagella; if these are located as a tuft at one end of the cell, this is described as lophotrichous (e.g. Chromatium), if they are distributed all over the cell, as peritrichous.
Flagella consist of a hollow, rigid cylinder composed of a protein called flagellin, which forms a filament anchored to the cell by a curved structure called the hook, which is attached to the basal body. Flagellae are, in effect, rotary motors comprising a number of proteinaceous rings embedded in the cell wall. These molecular motors are powered by the phosphorylation cascade responsible for generating energy within the cell. In action, the filament rotates at speeds from 200 to more than 1,000 revolutions per second, driving the rotation of the flagellum. The organization of these structures is quite different from that of eukaryotic flagella. The direction of rotation determines the movement of the cell. Periodically the direction of rotation is briefly reversed, causing what is known as a “tumble”, and results in reorientation of the cell. When anticlockwise rotation is resumed, the cell moves off in a new direction. Watch for the tumbles in this video. This allows bacteria to change direction. Bacteria can sense nutrients and move towards them - a process is known as chemotaxis. Additionally, they can also move away from harmful substances such as waste products and in response to temperature, light, gravity, etc. This apparently intelligent behavior is achieved by changes in the frequency of tumbles. When moving towards a favourable stimulus or away from an unfavourable one, the frequency of tumbles is low, thus the cells moves towards or away from the stimulus as appropriate. However, when swimming towards an unfavourable or away from a favourable stimulus, the frequency of tumbles increases, allowing the cell to reorient itself and move to a more suitable growth.
The second type of motility is shown by Spirochaetes, helical bacteria which have a specialized internal structure known as the axial filament which is responsible for rotation of the cell in a spiral fashion and consequent locomotion. The video shows highly motile Rhodospirillum rubrum cells. Watch the corkscrew motion of the cells through the medium.
The third mechanism is gliding motility. Gliding motility is the movement of cells over surfaces without the aid of flagella, a trait common to many bacteria. Gliding bacteria all secrete copious slime, but the exact mechanism which propels the cells is not known. The gliding motility apparatus which propels the cells involves a complex of proteins, yet the full nature of this “motor” and how the components interact is not understood. You can watch an Oscillatoria cell gliding in real time in the video.
However, beware for not everything that moves is motile! Under the microscope, motile bacteria seem to move in a purposeful way, though they may frequently change direction. However, even dead cells, such as those in this video, move. Rapid movement is due to capillary action or convection currents on the microscope slide. However, the motion which causes most problems is Brownian motion, first observed in 1827 by the English botanist Robert Brown. This is due to random molecular bombardment of tiny bacterial cells by the molecules of the solvent. A microbiologist needs to learn to distinguish the effects of Brownian motion from true bacterial motility.
The size of a cell is limited by the ability of nutrients and gasses to diffuse in and waste products to diffuse out, as well as for the cell constituents to get to where they are needed. The diffusion problem can be solved by adjusting the surface to volume ratios, and very thin or very flat cells could in theory be infinitely large, but this only makes the internal localization problem worse. Eukaryotic cells are 1-2 orders of magnitude larger that most prokaryotes, and they have managed to achieve these sizes by developing sophisticated nutrient uptake systems, subcellular compartmentalization, and the use of a cytoskeleton to transport vesicles and proteins around the cell. Large bacterial cells maintain high surface-to-volume ratios by being long and slender, or if spherical, contain an intracellular vacuole to press the cytoplasm into a thin layer just under the outer membrane. Some big prokaryotes also have a type of cytoskeleton and extensive intracellular membranes reminiscent of eukaryotic cells.
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The genus Epulopiscium is an unusual group of cigar-shaped Gram-positive organisms which live in the guts of fish. The name Epulopiscium means “guest at a fish’s banquet”. That may not be your idea of a cozy nest, but they seem to do very well there, growing up to nearly a millimetre in length, big enough to see with the naked eye - about the size of a grain of salt and a million times bigger than Escherichia coli. Why does a bacterium want to be so big? Possibly to escape being eaten by protists, which tend to be quite fussy about the particle size of the organisms they consume. While most bacteria reproduce by binary fission (dividing into two equal-sized daughter cells), Epulopiscium species produce offspring internally, usually two, one at each end of the cell. These new cells grow within the mother cell’s cytoplasm until it eventually bursts open and releases them.
You might think that such an unusual bacterium would have an unusual genome, but the fact that no Epulopiscium species currently grows in laboratory culture has slowed down research into this area. A recently published paper gets around this problem by using quantitative PCR to count the copy number of genes in individuals and in DNA extracted from populations of Epulopiscium cells isolated from the intestinal tract of the unicornfish Naso tonganus - now that’s what I call an ecological niche (Extreme polyploidy in a large bacterium. 2008 PNSA USA 105: 6730-6734). The results show that Epulopiscium is highly polyploid throughout its life cycle, and that individual cells contain tens of thousands of copies of its genome. A single Epulopiscium cell may contain up to 250 picograms of DNA, a massive amount compared with 6 picograms of DNA in a human cell, and this represents 50,000-120,000 copies of the genome. Genome copy number is positively correlated with cell size, with the largest cells containing the most DNA. Although other bacteria are known to possess multiple genomes, polyploidy of the magnitude observed in Epulopiscium is unprecedented. The arrangement of the genomes around the cell periphery may permit regional responses to local stimuli, helping Epulopiscium to maintain its unusually large size. By copying its genome thousands of times and arranging it just under the cell membrane, Epulopiscium may be more able to respond quickly and locally to stimuli which come in contact with the cell. This arrangement may give an Epulopiscium cell the advantages of social microbes, with additional benefits such as exceptional motility and enhanced resistance to predation normally found in large eukaryotic microbes or multicellular organisms.
Over the past week, international news stories have concentrated on the devastating cyclone in Burma (Myanmar), and the almost certain consequence of disease outbreaks in the aftermath. But at the same time, there’s another microbiology story unfolding in East Asia. Beginning in March, a large outbreak of hand, foot and mouth disease (HFMD) was reported from Fuyang city in Anhui Province in China. Note that HFMD is a human disease caused by enteroviruses belonging to the picornavirus family, but is not the same as the animal disease foot and mouth (FMD) caused by a different kind of picornavirus.
HFMD usually affects infants and children, is quite common worldwide and can be caused by a number of different enteroviruses. It is highly contagious and is spread through direct contact with the mucus, saliva, or faeces of an infected person. Like other enterovirus infections (including polio), HFMD typically occurs in small epidemics, usually during the summer and autumn months with an incubation period of 3-7 days.
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Enterovirus infections are common and occur worldwide. Although many infections show no symptoms and often go unnoticed, these viruses are also associated with occasional outbreaks in which a larger than usual number of patients develop clinical disease, sometimes with fatal consequences. The current outbreak is one of these. Initial testing for a variety of respiratory diseases did not reveal any conclusive results, but on April 23, the presence of Enterovirus (EV71) was confirmed. As of May 8th, at least 30 deaths had been reported and the disease had spread to 11 cities and several provinces across China. In all the fatal cases, which represent less than 1% of the thousands of children infected, the victims died with serious complications such as neurogenic pulmonary oedema (breathing difficulties reminiscent to those seen in polio victims).
Enterovirus replication begins in the gastrointestinal or respiratory tract but once the virus is present in the bloodstream may affect various tissues and organs, causing a variety of diseases. Clinically, it is difficult to distinguish the specific cause of most enterovirus infections. Diagnostic testing for non-polio enteroviruses requires specialized laboratory facilities. Diagnosis is made by detecting virus in the throat, in faecal samples or, more convincingly, from specimens collected from the affected part of the body, for example, cerebrospinal fluid (CSF) or biopsy material. A four-fold rise in the level of neutralizing antibody in specimens collected during the acute and convalescent phases of illness provides the best evidence for a recent infection. No specific antiviral agents are currently available for treatment of enterovirus infections, although intravenous administration of immune globulin may have a use in preventing severe disease in immunocompromised individuals or those with life-threatening disease.
EV71 was first isolated in an outbreak of neurological disease in California in 1969. One of the nastier enteroviruses, EV71 has been associated with several epidemics of severe neurological disease in children, mostly in East Asia. An outbreak in Taiwan in 1998 resulted in 129,106 reported cases, 405 children hospitalized and more than 80 deaths. EV71 appears to be emerging as an important virulent neurotropic enterovirus just as poliomyelitis is nearing eradication, but little is known about the molecular mechanisms of host response to EV71 infection.
Transmission of enterovirus infections is increased by poor hygiene and overcrowded living conditions. Improved sanitation and general hygiene are important preventive measures. Measures that can be taken to avoid getting infected with enteroviruses include frequent handwashing, especially after nappy (diaper) changes or going to the toilet, disinfection of contaminated surfaces with bleach, and washing soiled articles of clothing. Enteroviruses are quite resistant to many disinfectants so it is important to use chlorinated (bleach) or iodized disinfectants. During recognised epidemics, it may be advised to close institutions such as schools or child care facilities in order to reduce transmission among young children. Chinese public health experts currently predict that the number of cases will continue to increase and peak around June-July.
Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come into contact with during our history (History of human parasitology. Clin Microbiol Rev 2002 15: 595-612). The best-documented parasitic disease known from ancient times is caused by the nematode worm Dracunculus medinensis. The earliest description is from an Egyptian papyrus from 1500 BC that refers to both the nature of the infection and to techniques for removing the worm. Confirmation of the presence of this worm in ancient Egypt comes from the finding of a well-preserved worms in Egyptian mummies. Dracunculiasis, or Guinea worm disease, is one of the few diseases unambiguously described in the Bible, and most parasitologists accept that the “fiery serpents” that struck down the Israelites in the region of the Red Sea after the Exodus from Egypt somewhere between 1250 to 1200 BC were actually Guinea worms.
The adult worms live in the subcutaneous connective tissues of their victims, from which the females emerge to release thousands of larvae into water, where they are taken up by intermediate hosts, tiny aquatic crustaceans called Cyclops. In these hosts they mature into infectious larvae that infect humans when the crustaceans are accidentally swallowed in contaminated drinking water. On maturity, the large female worm, up to nearly a metre in length, protrudes from the skin, usually of the leg, and causes intense inflammation and irritation. The effects of the disease are crippling. Its victims develop large ulcers, usually in the lower leg. The ulcers swell, sometimes to the size of a tennis ball, and burst, releasing the spaghetti-like parasitic worm. Victims experience a pain so excruciating that they say it feels as if their leg is on fire. The searing pain compels people to jump into water, often the community’s only source of drinking water, to relieve the pain. When the infected person immerses his or her leg in the water, the worm in the leg releases thousands of larvae. The larvae are then ingested by Cyclops that live in the water. Thus the cycle begins again - when people drink the water, they are in effect drinking in the disease.
The most common way to treat Guinea worm disease involves wrapping the worm around a stick. This treatment has been employed for millennia and may have inspired the Rod of Asclepius which historically has symbolized the medical profession. As the adult worm begins to emerge from the patient’s skin, it is wound around a stick, then further extracted by a few centimeters per day. This slow process can take days or even weeks, but it is required to avoid breakage and leaving behind a portion of the worm. Leaving a portion of the dead worm remain within the host’s body increases the risk of infection, and can trigger immune responses resulting in pain and swelling. In many countries, a broken worm is immediately removed surgically, or the worm can be excised surgically from the very beginning if health care facilities are available. Antihelminthic drugs such as metronidazole or thiabendazole are sometimes used in conjunction with physical extraction. However, one study found that antihelminthic therapy was associated with aberrant migration of worms, resulting in infection in areas other than the lower extremity.
Dracunculiasis is a classic example of a neglected tropical disease, a symptom of poverty and disadvantage. Those most affected are the poorest populations often living in remote, rural areas, urban slums or in conflict zones. With little political voice, neglected tropical diseases have a low profile and status in public health priorities. In 1997 the World Health Assembly pledged to completely eradicate Guinea worm disease. This is no small task, but there are several factors which make eradication a possibility. Dracunculiasis is the first parasitic disease targeted for eradication because:
Diagnosis is easy and unambiguous (presence of an emerging adult worm).
The transmission agent, Cyclops, is not a mobile vector as is a mosquito.
The incubation period in both Cyclops and humans is of limited duration.
Interventions are effective, low cost, and relatively simple to implement.
The disease has a limited geographic distribution and is seasonal in nature.
Success in eliminating the disease has been demonstrated in several countries in Asia and the Middle East.
There is no known animal reservoir.
Is Dracunculiasis eradication close? In 2007 the WHO announced that Guinea worm disease now affects around 25,000 people in nine countries, compared with an estimated 3 million people were infected in over 20 countries in the early 1980s. Twelve countries were declared Guinea worm-free in early March. If progress continues at this rate, the disease could be eradicated in less than two years. It is probable that complete eradication will take quite a few years yet, although it should be possible to eliminate the disease from seven countries in a couple of years, leaving only two endemic countries, Sudan and Ghana (Dracunculiasis eradication by 2009: will endemic countries meet the target? Tropical Medicine & International Health 2007 12: 1403-1408). One lesson to be drawn from the problems of local ownership and the experience of cash rewards is that there are dangers in throwing money at the problem. While the eradication initiative badly needs additional resources, it needs them at such a level and managed in such a way that they do not distort the priorities of the health care system, or exceed the capacity of local staff to manage them. The amounts needed are not large, but their continuity and flexibility is important. Given the highly seasonal transmission of dracunculiasis, the resources must be available at very specific times of the year, which is not always achieved. In spite of the difficulties, complete worldwide eradication of this ancient disease is drawing nearer.
Magnetic or “magnetotactic” bacteria were first discovered in the 1960s, and naturally organize themselves in the direction of Earth’s magnetic field, as shown in this video:
Inside these bacteria there is a row of iron-containing crystals aligned with the long axis of the cell, giving them the equivalent of an internal magnetic compass needle (Molecular mechanisms of magnetosome formation. Ann Rev Biochem 2007 76: 351-66). Such bacteria can sense and align themselves relative to the earth’s magnetic field. Magnetotactic bacteria are major constituents of many natural microbial communities, especially in aquatic habitats. There is a broad range of shapes and groups of magnetic bacteria. However, cultivation of these organisms in the laboratory is often difficult and only few strains of magnetotactic bacteria have been isolated in pure culture, a tiny minority of the vast diversity of naturally occurring populations from largely unexplored natural habitats such as the marine environment.
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So why would bacteria want to be magnetic? Leaving aside the possibility that they are magnetic by accident, e.g. as a consequence of some metabolic byproduct, the truth is that we really don’t know the reason. However, the most likely explanation lies not in north-south alignment, but in up and down. The magnetotactic bacteria we know about require low but very precise levels of oxygen to survive, and must live in sediments where the oxygen concentration is just right for their needs. Over much of the globe, the Earth’s magnetic field actually points down towards the centre of the planet, so by following these lines of magnetic flux, they are able to ensure that they bury themselves in the sediment, which is exactly where they want to be. Thus the majority of magnetotactic in the Northern Hemisphere are north seeking, and those in the Southern Hemisphere are south seeking.
Viroporins are virus-encoded proteins that participate in virus replication, including the promotion of release of virus particles from cells (Viroporins. FEBS Lett 2003 552: 28-34). They also affect cellular functions, including the cell vesicle system, glycoprotein trafficking and membrane permeability. Viroporins are usually not essential for the replication of viruses, but their presence enhances virus growth. Composed of 60-120 amino acids, viroporins have a hydrophobic transmembrane domain that interacts with lipid bilayers, and polymerization of viroporin monomers creates hydrophilic pores in the membranes of virus-infected cells. Viroporins are present in tiny amounts in the virus particles (virions) of many animal RNA viruses, e.g. influenza A virus M2 protein, poliovirus 2B and 3A proteins, HIV Vpu and SARS coronavirus E protein. Viroporins contribute to the pathology of virus diseases by altering membrane permeability and disrupting ion homeostasis in infected cells.
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A paper recently published in Cellular Microbiology reports that viroporins of hepatitis C virus, poliovirus and other animal RNA viruses induce apoptosis in host cells (Viroporins from RNA viruses induce caspase-dependent apoptosis. 2008 Cell Microbiol 10: 437-451). In addition to their capacity to disrupt ionic cellular homeostasis and promote cell lysis, the expressed viroporins were able to induce cell death. Degradation of DNA and generation of apoptotic bodies were observed on viroporin expression. Activation of caspase-3, altered mitochondrial morphology and detection of cytochrome c release from mitochondria suggests involvement of the mitochondrial pathway in viroporin-induced apoptosis and shows that viroporins induce caspase-dependent programmed cell death.
It is possible that viroporins have different effects depending on the level of expression and/or the host-cell type. The induction of apoptosis in host cells by viruses is common and could assist virus spread. The next step in understanding the links between viroporins and apoptosis will be to unravel the mechanisms by which viroporins trigger apoptotic pathways and to demonstrate that these findings are relevant during virus infections.
