91 posts · 70,998 views
The idea of the blog was to provide accurate and interesting information and reflections on science from somebody currently in the field.
There is more than one type of genetic material within the cell. As well as DNA, which stores the code for making cellular protiens, there is also RNA, which contains similar snatches of code but is less stable and more mobile than DNA. If DNA is a library of books which are not allowed to be removed, then RNA is little buts of paper containing copies of pages that are spread around for people to read.... Read more »
Mann B, van Opijnen T, Wang J, Obert C, Wang YD, Carter R, McGoldrick DJ, Ridout G, Camilli A, Tuomanen EI.... (2012) Control of Virulence by Small RNAs in Streptococcus pneumoniae. PLoS pathogens, 8(7). PMID: 22807675
One thing that becomes more clear with each piece of research is that the human body is a hive of mostly harmless bacteria that live in any crevice they can reach while affecting their human host as little as possible. In some cases these bacteria can be very beneficial – preventing more dangerous bacteria from taking up residence in places like the stomach and throat. In some cases they can occasionally go rogue, get into places they shouldn’t be, and cause havoc.... Read more »
Kjersti Aagaard, Kevin Riehle, Jun Ma, Nicola Segata4, Toni-Ann Mistretta, Cristian Coarfa, Sabeen Raza, Sean Rosenbaum, Ignatia Van den Veyver, Aleksandar Milosavljevic, Dirk Gevers, Curtis Huttenhower, Joseph Petrosino, James Versalovic. (2012) A Metagenomic Approach to Characterization of the Vaginal Microbiome Signature in Pregnancy. PloS one, 7(6). DOI: 10.1016/j.ajog.2010.10.087
Maria G. Dominguez-Bello, & et al. (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proceedings of the National Academy of Sciences, 107(26). DOI: 10.1073/pnas.1002601107
In multicellular organisms it is essential that every cell behaves and does the job it was produced to perform. The survival of a multicellular organism depends on this - every cell in your body is tightly controlled in terms of how big it can grow (fairly big), when it can reproduce (almost never) and what sort of metabolic processes it may carry out. And, like a dystopian sci-fi future, any cell that steps out of line is put to death. Not by surrounding cells, but by it’s own internal processes.... Read more »
Robinson, R. (2012) In E. coli, Interrupting One Death Pathway Leads You Down Another. PLoS Biology, 10(3). DOI: 10.1371/journal.pbio.1001278
I’ve written before about ancient diseases of the ice age, but this time I’m going even further back in time, to diseases that were present in the first human-like hominids. Although many human infections only developed after human settlements and animal domistication, early human ancestors would still have been fighting off bacteria and other nasty diseases. Some of these diseases are still around today.... Read more »
Trueba G, & Dunthorn M. (2012) Many neglected tropical diseases may have originated in the Paleolithic or before: new insights from genetics. PLoS neglected tropical diseases, 6(3). PMID: 22479653
Monot, M., Honoré, N., Garnier, T., Zidane, N., Sherafi, D., Paniz-Mondolfi, A., Matsuoka, M., Taylor, G., Donoghue, H., Bouwman, A.... (2009) Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nature Genetics, 41(12), 1282-1289. DOI: 10.1038/ng.477
Diavatopoulos DA, Cummings CA, Schouls LM, Brinig MM, Relman DA, & Mooi FR. (2005) Bordetella pertussis, the causative agent of whooping cough, evolved from a distinct, human-associated lineage of B. bronchiseptica. PLoS pathogens, 1(4). PMID: 16389302
I’ve written before about the many ways that bacteria can move around. Considering that they’re just one cell long, micro-organisms have a whole range of ways to travel through their little world. Movement is useful for finding food and for changing your environment when all nearby resources have been exhausted. For bacteria that can’t move, however, or that don’t want to move, there is a second option; they can park themselves on a nearby surface and settle down to wait.... Read more »
Busscher HJ, & van der Mei HC. (2012) How do bacteria know they are on a surface and regulate their response to an adhering state?. PLoS pathogens, 8(1). PMID: 22291589
I’ve been getting so exited about the awesome powers of bacteria on this blog lately that I’ve been neglecting to cover the nasty bacteria. More specifically the fascinating world of antibiotics, the antimicrobial elements that bacteria and fungi produce and that humans exploit, manufacture and synthesise in order to protect against bacterial infections.... Read more »
Toprak, E., Veres, A., Michel, J., Chait, R., Hartl, D., & Kishony, R. (2011) Evolutionary paths to antibiotic resistance under dynamically sustained drug selection. Nature Genetics, 44(1), 101-105. DOI: 10.1038/ng.1034
Antibiotic resistance is often seen as a modern phenomenon – an ability generated by bacteria in order to defend against the challenges of modern medicine. This is supported by the fact that bacteria from before the era of antibiotics are often more susceptible to their use. Which is why I found it intriguing that recent studies (ref below) have unearthed bacteria from 30 000-year old permafrost sediment and have found evidence of genes that provide resistance against three of the most common types of antibiotics used in hospitals: β-lactam, tetracycline and glycopeptide antibiotics.... Read more »
The human immune system is a large and complex beast, but in general it has two roles. Firstly, to prevent an infection from causing any harm and secondly to protect the body against a repeat attack. For many diseases protection against reinfection happens very efficiently, and this is the principle on which vaccines are based. By exposing your body to a non-harmful sample of the disease your immune system can built up resistance. For cytomegalovirus however the immune system seems mysteriously unable to protect against reinfection, which is a major problem for the design and development of working vaccines.... Read more »
Hansen, S., Powers, C., Richards, R., Ventura, A., Ford, J., Siess, D., Axthelm, M., Nelson, J., Jarvis, M., Picker, L.... (2010) Evasion of CD8 T Cells Is Critical for Superinfection by Cytomegalovirus. Science, 328(5974), 102-106. DOI: 10.1126/science.1185350
Nigro, G., Adler, S., La Torre, R., & Best, A. (2005) Passive Immunization during Pregnancy for Congenital Cytomegalovirus Infection. New England Journal of Medicine, 353(13), 1350-1362. DOI: 10.1056/NEJMoa043337
This is the first time in ten years that I haven't had an exam around summer-time. It feels odd, everyone around me is either exam-stressed or post-exam-relaxed, it's turning to summer and there's a definite final term feeling but this time I'm not really part of it. It's been an interesting year this year, since January I've not been involved in any part of research science, other than writing about it.However luckily I'm still surrounded by lectures, seminars, talks and various other interesting stuff which no one seems to mind me occasionally turning up too. Seeing as I haven't written much about virus's lately I headed over to a talk the other day about Marek's disease, which is caused by a Herpes Virus and has a rather devastating affect on chickens.It makes them stand like this :(It started back in the sixties, when rather a lot of chickens suddenly started dropping dead, sometimes up to 50% of all the stock in a large barn. Bear in mind these weren't the happy pecking-around-shrubs-of-grass chickens that feature on the front of free-range eggs, but rather a lot of chickens quite closely packed inside a big barn. The cause was found to be MDV - Marek's disease virus. After a lot of work a vaccination was found and given to all the chickens. Over $2 billion was saved by this, and the chickens were able to survive, right up until they got slaughtered for food.But then, around the 1980s the disease suddenly reared it's head again, this time in a far more virulent form imaginatively labelled vvMDV (which stands for very virulent MDV). More research, another vaccine, and the deaths stopped.Until just before 2000 when the virus evolved again into an even more virulent strain called vv+MDC, which means exactly what you think it does. Another vaccine was made (called Rispens) but at this point it was becoming fairly clear that this virus was behaving oddly. Three times it had changed, becoming more and more deadly each time:Image from the presentation slides showing the development of new strains with an increase in virulence.This is not normal behaviour. Virus's rely on their hosts, they can't replicate, survive or do anything without a host cell, which means they have a vested interest in keeping the host alive. If anything, viral strains should evolve to become less virulent; a virus that kills the host will be a virus without a host and is therefore less likely to survive and propagate than a virus with a host.It turns out in this case that the evolution of increase virulence is down exclusively to the way the vaccine interacts with the virus. The virus works by being inhaled into the chickens lungs, getting into the cells of the immune system (B and T cells) and causing a latent infection of the lymphocytes (T cells). Virus cells can also work their way to the epithelial cell of the feather follicles and will shed from under the feathers, thus keeping the virus in circulation.In an ideal situation a vaccine would produce what is known as "sterilising immunity", where use of the vaccine kills all viruses dead. This is how almost all human vaccines work. With the Marek's disease vaccine however, the virus was not killed completely, but could still replicate and shed from the feathers. This means that the virus was still within the system, able to change and evolve. The vaccine however, does make the virus less likely to spread, which means that a more virulent form that the vaccine does not protect against is able to outcompete the less virulent strain. Because the chickens are all in very close proximity, and because there are a lot of them, the more virulent strain can spread much faster throughout the population. With normal chickens, in small isolated populations this would not happen as a virus that virulent would run out of host and die out.This creates a paradox - vaccines are needed to stop the chickens getting the virus, but at the same time use of the vaccine is creating an evolutionary environment in which a more virulent virus can grow. There are some responses to avoid this though. Firstly, to develop a virus that produces sterilising immunity, i.e that kills all thee virus dead. Secondly, to allow the chickens more room and freedom to stop the virulent strains spreading so quickly. And while this second solution sounds like every animal-rights campaigner's dream, remember that it only really works if very few people in the world eat chicken. In reality there are lots of people, and a limited space for chickens - eating chickens which have lead a happy healthy life is a privilege for a few, not the reality for the majority.---Witter RL (2001). Protective efficacy of Marek's disease vaccines. Current topics in microbiology and immunology, 255, 57-90 PMID: 11217428Witter RL (1997). Increased virulence of Marek's disease virus field isolates. Avian diseases, 41 (1), 149-63 PMID: 9087332---Follow me on Twitter!
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Witter RL. (1997) Increased virulence of Marek's disease virus field isolates. Avian diseases, 41(1), 149-63. PMID: 9087332
In posts one and two of this mini-series I explored how plants can defend against bacteria by releasing dangerous chemicals and by killing off cells. This post looks at how surviving one bacterial attack can make plants more able to survive subsequent ones with both local and systemic acquired resistance.Locally acquired resistance is the simplest to manage, and provides a clear advantage. If cells have been attacked once it makes sense to defend them in case of a second attack. Plants achieve this by strengthening the cell walls in cells that have survived the bacterial attack. Experiments adding elicitors (bits of bacteria that stimulate the plant pathogen receptors) to plant cells showed that proteins in the cell wall became oxidatively cross-linked as they sense the bacteria. Interestingly the molecule responsible for this is hydrogen peroxide, one of the molecules also involved in the cell-death response discussed in post two. If it doesn't kill the plant, it makes it stronger.The cell membrane is the blue box at the bottom, whereas the cell wall is the light blue rods in the middle. It is the cell wall which is strengthened. Image from wikimedia commons.This response is all very well for plant cells which happened to be near the site of infection, but what about the rest of the plant? Is it possible for cells on the other side of the plant to be warned and ready for a pathogen attack? Despite the inability of plant cells to move, the answer surprisingly is yes. Cells at the site of infection can release a chemical called salicylic acid which moves through the plants vascular system (the system which also delivers sugars and other important nutrients to all parts of the plant).The chemical structure of salicylic acid, which is chemically similar to the active component of aspirin. Following an infection, the levels of salicylic acid were found to rise dramatically in cells around the zone of infection, before spreading through the rest of the plant. This isn't a species specific response either but one found in many different species; grafting parts of one plant onto another did not stop either plant from acquiring resistance. In response to the salicylic acid signal cells start accumulating small amounts of hydrogen peroxide, which can lead to the same cell wall strengthening seen around the area of infection.As well as salicylic acid it has also been suggested that infected areas of the plant can release the volatile molecule methyl salicylate, commercially known as oil of wintergreen. Rather than travelling through the plant this signal is airborne, allowing transmission not just to other parts of the plant, but to neighbouring (and therefore likely to be related) plants as well. As the only difference between these two signalling molecules is the addition of a small CH3 group, the methyl salicylate can easily be converted back into salicylic acid once it reaches the cells where it can cause the same downstream response.If anyone was wondering quite why I've suddenly been into plants part of the reason is that the BBC is showing a program called "Botany - a blooming history" and I've been catching the episodes. Despite the slight naffness of the title, it's actually a really good program showcasing experiments, personalities, and the scientific method as it unfolds the history of plant science. You can catch the episodes here on iPlayer.---Brisson, L., Tenhaken, R., & Lamb, C. (1994). Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance The Plant Cell, 6 (12) DOI: 10.2307/3869902Durrant, W., & Dong, X. (2004). SYSTEMIC ACQUIRED RESISTANCE Annual Review of Phytopathology, 42 (1), 185-209 DOI: 10.1146/annurev.phyto.42.040803.140421... Read more »
Brisson, L., Tenhaken, R., & Lamb, C. (1994) Function of Oxidative Cross-Linking of Cell Wall Structural Proteins in Plant Disease Resistance. The Plant Cell, 6(12), 1703. DOI: 10.2307/3869902
Shulaev, V., Silverman, P., & Raskin, I. (1997) Airborne signalling by methyl salicylate in plant pathogen resistance. Nature, 385(6618), 718-721. DOI: 10.1038/385718a0
The first post of this mini-series covered how plants can defend themselves against bacterial attack by releasing chemicals, either on a regular basis or as a specific response to the attack. This post will explore the hypersensitive response, which allows plants to rapidly kill of cells around the area of infection, starving the bacteria of nutrients to prevent it spreading. The end result is a small area of dead plant matter, with the rest of the organism unaffected.One of the main differences between plants and animals that I flagged up in the last post is that plant cells don't move. The use of the hypersensitive response shows another; plants have a very non-determinant structure. Animals will grow towards a clear well defined shape and once they get it, they stick with it. Your body does change as you grow older, but it's not about to grow an extra leg. Plants on the other hand may have determinant structures within them, such as leaves or flowers, but the overall organism can just keep growing for as long as it needs to. If a leaf is lost through disease, the plant can just grow a new one, or several new ones.These leaves are expendable. Your arm is not. Image from wikimedia commons.Because of its non-determinant nature it is a lot easier for the plant to kill parts of itself off in order to stop an infection spreading. One way that the hypersensitive response does this is by the production of large numbers of reactive oxygen species in cells surrounding the site of infection. These include hydrogen peroxide, and various hydroxide and oxygen containing free radicals. Free radicals are species with one unpaired electron and therefore are extremely reactive and extremely dangerous. These free radicals lead to chain reactions that can break down lipids in the membrane, inactivate enzymes and generally roll around like a loose canon causing havoc within the cell.As well as reactive oxygen species, the cell also experiences large ion fluxes, as potassium and hydroxide ions flood into the cell and hydrogen and calcium ions flood out. These result in the cell releasing any stored toxic compounds it might have (which may also help to kill the bacteria) and may serve to integrate the mitochondria into the process of cell death (see reference one). As mitochondria are crucial in coordinating the programmed cell death of animal cells it would be surprising if they did not play some part in the controlled destruction of plant cells. The actual sequence of destruction varies from plant to plant, but the overall result is the same, and area of dead plant tissue within the still healthy surviving plant.A leaf infected with tobacco mosaic virus, showing lighter areas of dead leaf interspersed with the green areas of normal growth. Image from wikimedia commons.The plant hypersensitivity response can (if you want it to) be considered analogous to the human innate immune response, in that it occurs directly in response to a bacterial attack, and it occurs only at the site of bacterial infection. Plants, however, also have ways of making more long-term changes to protect against bacterial attacks in the future both at the site of the old reaction and throughout the whole plant. How the plant achieves this, without any cellular movement, will be the topic of the final post in this mini-series.---Lam, E., Kato, N., & Lawton, M. (2001). Programmed cell death, mitochondria and the plant hypersensitive response Nature, 411 (6839), 848-853 DOI: 10.1038/35081184Pontier, D., Balagué, C., & Roby, D. (1998). The hypersensitive response. A programmed cell death associated with plant resistance Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 321 (9), 721-734 DOI: 10.1016/S0764-4469(98)80013-9Taiz, Zeiger, Plant Physiology, third edition Sinauer Associates 2002.---Follow me on Twitter!
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Lam, E., Kato, N., & Lawton, M. (2001) Programmed cell death, mitochondria and the plant hypersensitive response. Nature, 411(6839), 848-853. DOI: 10.1038/35081184
Pontier, D., Balagué, C., & Roby, D. (1998) The hypersensitive response. A programmed cell death associated with plant resistance. Comptes Rendus de l'Académie des Sciences - Series III - Sciences de la Vie, 321(9), 721-734. DOI: 10.1016/S0764-4469(98)80013-9
Although I've never officially studied immunology, my second year course in Pathology left me with a pretty solid idea of how humans defend themselves against bacterial attack. Even without a university course I've always been vaguely aware of the presence of immune cells; the B and T cells that make up the adaptive immune system, the clotting response, and the symptoms of inflammation around the site of infection.How plants responded to bacterial attack was still a complete mystery though. One of the main things that distinguishes plants from animals is that animal cells are a lot more motile, they can move through the body. Animal cell movement is crucial during the development of the embryo and even once the body is fully formed cells still rush around the blood stream and slide around in the epithelial layers. The correct functioning of the immune system relies on cells being able to do this, T cells will pick up bits of bacteria at the site of infection and go running back with them to the lymph nodes which will start organising the best way to deal with the infection.A macrophage in the lungs, from Wikimedia commons. The macrophage engulfs bacteria and eats them, which requires it to be able to move.With a few odd exceptions plant cells do not move. Not at all. There is no movement of cells during the seed development, and even the movement of plants towards sources of light and water is caused by cells growing rather than moving. How then does the plant respond and react to bacterial infections?There are several different ways, which is why this is a three-part post series: 1-Deadly Chemicals 2-Honourable Suicide 3-Acquired Resistance.Part One: Deadly ChemicalsOne of the simpler ways to remove a bacterial infection is to release a chemical that is harmful to the bacteria. There are quite a lot of plants that produce antibacterial products as normal secondary metabolites, an example of which is saponins, a group of compounds which have soap-like properties. As saponins are lipid soluble they can break up bacterial membranes by binding to sterol compounds within the membrane and disrupting the structure. Studies done on oats (reference one) have shown that reducing the natural levels of saponin made the oat plants much more vulnerable to fungal infections.Rather more excitingly, plants can also release certain chemicals in response to a bacterial attack. When bacteria attack plants have been shown to release an assortment of hydrolytic enzymes - glucanases, chitinases, etc that break down cell walls and membranes. These are known as pathogenesis-related proteins as they are specific to bacterial or fungal attack. One of the better researched is a group of chemicals called phytoalexins. In normal conditions neither the phytoalexins themselves, nor the enzymes used to make them, are found within plant cells. It is only after a microbial invasion that the enzymes are transcribed and translated and the phytoalexins synthesised.In order to respond specifically to bacterial attack, the plant needs to be able to recognise bacteria as invading elements. Like many animals, plants have what are known as "Toll-like receptors" that recognise bacterial pathogen molecules (which in animals are referred to as PAMPS Pathogen-Associated Molecular Patterns but in plants seem to be called elictors) such as bits of protein and polysaccharide fragments from the bacterial cell wall.Comparison of the plant and animal TOLL receptors. The blue and red lines are the receptors, and the blobs attached to them are the bits of pathogen. The yellow boxes labelled PK stand for 'protein kinase cascade' which carries the message through the cell to turn on the genes required. Diagram adapted from reference two.By recognising pathogens as they invade, the plant cells can launch a deadly chemical attack against them, without requiring any movement. None of this requires the cells to travel around, and until the bacteria develop resistance to the chemicals being used, it can be highly affective. Chemical warfare however, is only one of the strategies that plant cells can adopt to protect themselves against invading microorganisms, and my next post will cover the second - depriving the bacteria of valuable nutrients by committing cellular suicide.---1) Papadopoulou, K. (1999). Compromised disease resistance in saponin-deficient plants Proceedings of the National Academy of Sciences, 96 (22), 12923-12928 DOI: 10.1073/pnas.96.22.129232) Nürnberger, T., & Scheel, D. (2001). Signal transmission in the plant immune response Trends in Plant Science, 6 (8), 372-379 DOI: 10.1016/S1360-1385(01)02019-23) Taiz, Zeiger, Plant Physiology, third edition Sinauer Associates 2002.---Follow me on Twitter!
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Papadopoulou, K. (1999) Compromised disease resistance in saponin-deficient plants. Proceedings of the National Academy of Sciences, 96(22), 12923-12928. DOI: 10.1073/pnas.96.22.12923
This is the fourth post in my latest SGM series.
The social behaviour of bacteria is something that I get very excited about. From the wolf-pack hunting strategies of Myxococcus xanthus to the terminal differentiation of cyanobacteria, it's something that I never get tired of writing about. As well as providing interesting quirks of bacterial behaviour, living within a colony also gives new scope for exploring the evolution of bacteria; not just as single entities but as a fully functioning social group.
One of the differences of living within a social colony as opposed to alone means that altruistic-type behaviour has to be adopted. Bacteria living within a biofilm need to excrete the sticky goo that holds the biofilm together, which is problematic because synthesising and secreting goo takes up a lot of energy. So within this colony, there will be 'cheaters' - those bacteria that live in the surrounding goo produced by others, while making none themselves.
A bacterial biofilm, showing individual bacteria in green. Image taken from the FEI website, shown there courtesy of Paul Gunning, Smith & Nephew
As with all colonies, cheating might benefit the individual but has no benefit for the colony as a whole. Too many cheaters and there won't be any biofilm. And recently an even more subtle form of cheating has been shown within the biofilms of the bacteria Pseudomonas aeruginosa, with bacteria that don't just refuse to make vital sticky chemicals, but also abstain from the entire process of forming a biofilm.
Bacteria use a complex communication system called quorum sensing in order to determine how many other bacteria they are surrounded by. Once enough bacteria are present, all signalling their existence, the biofilm will start to form. However some bacteria isolated from the biofilm were shown not to be taking part in any quorum sensing at all. Quorum sensing appears to be quite a burden for a growing cell - cells with the quorum sensing genes knocked out tend to grow a lot faster that the socially conscious cells that allow biofilms to form.
The paper that goes through this (reference one) highlights it as a form of social cheating, with bacteria avoiding quorum sensing to benefit themselves while mooching off the quorum sensing behaviour of others. I'm not entirely certain that this is the case though. It may just be an good example of job allocation within the bacterial society. Clearly not all bacteria are required to be continually quorum sensing, so why should they all have to? Would it not be more sensible to have some exempt from that task, so that they can concentrate on growing, dividing, and spreading the colony? This may be more a case of tax-breaks than of benefit-cheats.
Social evolution doesn't just take place within species, but also between them, and like every other organism bacteria are in a constant state of coevolution with both their 'prey' and their predators. Most predator-prey interactions take long periods of time to study, but the beauty of bacteria is that you can go through several generations in the course of one week's growth. Studies of the bacteria Pseudomonas fluorescens and its bacteriophage parasite showed that both the bacteria and the bacteriophage evolved far quicker when interacting together than they did when competing against a non-changing opponent.
Bacteriophage surrounding a bacteria. Image from wikimedia commons
'Evolve' here means that the bacteria and the bacteriophage showed a greater change in their genetic makeup, and a greater genetic divergence from bacteria not pitted against the phages. Unsurprisingly, the genes that changed the most were those involved in host-phage interaction. This study (reference 2) is also a great example of the usefulness of whole genome sequencing. Whole populations of bacteria and phage were allowed to evolve both together and separately and then just sent away for sequencing with the results analysed at the end.
You really can't be an anti-evolutionist while studying bacteria. They just do it so damn quickly and often you can see it happening.
---Sandoz, K., Mitzimberg, S., & Schuster, M. (2007). From the Cover: Social cheating in Pseudomonas aeruginosa quorum sensing Proceedings of the National Academy of Sciences, 104 (40), 15876-15881 DOI: 10.1073/pnas.0705653104
Paterson S, Vogwill T, Buckling A, Benmayor R, Spiers AJ, Thomson NR, Quail M, Smith F, Walker D, Libberton B, Fenton A, Hall N, & Brockhurst MA (2010). Antagonistic coevolution accelerates molecular evolution. Nature, 464 (7286), 275-8 PMID: 20182425
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Sandoz, K., Mitzimberg, S., & Schuster, M. (2007) From the Cover: Social cheating in Pseudomonas aeruginosa quorum sensing. Proceedings of the National Academy of Sciences, 104(40), 15876-15881. DOI: 10.1073/pnas.0705653104
Paterson S, Vogwill T, Buckling A, Benmayor R, Spiers AJ, Thomson NR, Quail M, Smith F, Walker D, Libberton B.... (2010) Antagonistic coevolution accelerates molecular evolution. Nature, 464(7286), 275-8. PMID: 20182425
This is the third post in my latest SGM series.One of the first topics that I learnt in Biology was that there are two types of things; living things, and dead things. Living things are given a whole host of distinguishing characteristics (growth, reproduction and, my favourite, irritability) where as dead things are defined as everything else. Biology was usually defined as the study of living things.As I grew older, I found that there were many complications to this neat little classification. Viruses - which are neither fully living, nor properly dead. A whole organism can be dead, despite the fact that many of its cells are still alive (how alive is a freshly killed animal? Or the flowers in a vase?). And of course what is for me the most intriguing case, that of dormant bacteria.Dormancy is an odd state to be in. A dormant organism shows none of the signs of being alive. It does not eat, grow or divide (although some very basic metabolic processes may still continue). It shows no response to any outside stimulus, and can often be placed in conditions that would lead the living organism to perish, such as extremes of temperature and pressure. Yet somehow just one simple stimulus can cause this previously dead looking organism to spring magically back into life.Bacteria are not the only things that can go dormant. Someanimals can as well, the most famous example being tardigrades -the thing shown on the right that looks a bit like a plushie made by Tim Burton (image from wikimedia commons). Yeast are well-known for forming dormant spores, and it can be argued that a seed is technically a dormant plant, just waiting for water to be added to bring it back to life.One of the most medically important dormant bacteria is Mycobacterium tuberculosis which infects humans and leads to TB. One of the reasons for its pathogenicity is that they can go dormant, both outside the body (which makes them hard to shift from a hospital) and inside the body, after the primary infection (which makes them even harder to shift from inside a human body).Although the latent cells can remain within the body for many years, sometimes never coming back from dormancy at all, ideally there should be some signal to bring them back to life. These signals are known as "resuscitation-promoting factors" or RFPs. These RFPs are required for virulence, and to bring the bacteria back from dormancy, but are not necessary for the growth and proliferation of cultures in the lab.Within human tissues, and throughout the cycle of the disease, you can track these RFPs to try and get an insight into what the bacteria is up too, and when it may move from latent periods to periods of active growth. As well as being useful for tracking the course of infection, this might also have therapeutic implications. If you can convince the bacteria not to come out of dormancy then you have an infection state that might not be completely curable but is at least controllable.How organisms survive in a state of dormancy, and indeed how they ever come out of it, is a subject I find really fascinating. I'm unlikely to ever get to do much research on it (because as fascinating as it might be screwing around with my little bugs till they do what I want is endlessly more fun) but I'll probably have a good few more posts writing about it and exploring how it works.---Kana BD, Gordhan BG, Downing KJ, Sung N, Vostroktunova G, Machowski EE, Tsenova L, Young M, Kaprelyants A, Kaplan G, & Mizrahi V (2008). The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Molecular microbiology, 67 (3), 672-84 PMID: 18186793Davies AP, Dhillon AP, Young M, Henderson B, McHugh TD, & Gillespie SH (2008). Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue. Tuberculosis (Edinburgh, Scotland), 88 (5), 462-8 PMID: 18440866
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Kana BD, Gordhan BG, Downing KJ, Sung N, Vostroktunova G, Machowski EE, Tsenova L, Young M, Kaprelyants A, Kaplan G.... (2008) The resuscitation-promoting factors of Mycobacterium tuberculosis are required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Molecular microbiology, 67(3), 672-84. PMID: 18186793
Davies AP, Dhillon AP, Young M, Henderson B, McHugh TD, & Gillespie SH. (2008) Resuscitation-promoting factors are expressed in Mycobacterium tuberculosis-infected human tissue. Tuberculosis (Edinburgh, Scotland), 88(5), 462-8. PMID: 18440866
This is the second post from my latest SGM series.It's a pretty well known fact now that the human body contains lots of bacteria. Bacteria live on your skin and in your throat and gut, for the most part completely harmlessly, protecting your body from more dangerous invaders.But something that doesn't get mentioned quite so often is that humans are not the only animals with a corresponding posse of bacteria. Other animals have them as well, including insects. From a bacterial point of view both your body and an insect's body are merely new lands to be colonised, and if they can colonise those lands without totally destroying them, then so much the better.Like human bacteria, some bacteria that live within insencts have formed a symbiotic relationship, where the insect relies on the bacteria for survival. The pea aphid (shown to the right - photo by Marlin E. Rice) contains a symbiotic bacteria, Buchnera aphidicola that is required to produce one of the major amino-acids used to make important proteins. Completely sequencing the genome of the aphid shows that it does not contain the gene for argenine; it requires the Buchnera to make it. Likewise the sequenced bacterial genome lacks the genes for animo-acid deregulation, and several other minor amino acids. It gets these from its insect host. The bacteria lives within the host, in specialised little cells, and is passed down from mother aphid to daughter as without it the aphids will not survive.This raises important questions about the control of the genetic activity of both the bacteria and the insect. If the insect needs more argenine, it must have a way of telling the bacterial genome to produce it, likewise if the bacteria requires more of the non-essential amino-acids it needs to be able to push the insect to make them. Modeling flux pathways for the creation and degredation of some of these amino acids helps to build up a picture of how this control can function, at a metabolic level if not a genomic one. The flux analysis also shows how important this symbiotic relationship is, for both the bacteria and the insects.Leaf cutter ants (shown on the left - image from Wikimedia commons) have what is possibly the most complex and fascinating of interactions with microorganisms. For a start, they harvest fungi growing it in little gardens and feeding it with mashed up plants. This fungi can be susceptible to infections, so the ants also need to provide pesticides to keep their crops alive. As ants have not quite reached the level of large scale chemical manufacture, they have to rely on symbiotic bacteria to produce the antibacterial and antifungal compounds they need. The bacteria they use are species of Pseudonocardia and Streptomyces which produce a large number of secondary metabolites that can be used to destroy the fungal-infectors. The ants excrete these secondary metabolites in their waste, which can then be moved into the fungal garden. The bacteria also showed some anti-fungal activity against the fungus growing in the gardens, so could be used to control how far the crop spreads.I'm always wary of ants, I certainly got bitten by them enough times as a kid. With their little societies and gardens and wars and multistory-housing compexes they are scarily human for a tiny piece of exoskeleton with legs.---Wilson AC, Ashton PD, Calevro F, Charles H, Colella S, Febvay G, Jander G, Kushlan PF, Macdonald SJ, Schwartz JF, Thomas GH, & Douglas AE (2010). Genomic insight into the amino acid relations of the pea aphid, Acyrthosiphon pisum, with its symbiotic bacterium Buchnera aphidicola. Insect molecular biology, 19 Suppl 2, 249-58 PMID: 20482655Thomas GH, Zucker J, Macdonald SJ, Sorokin A, Goryanin I, & Douglas AE (2009). A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola. BMC systems biology, 3 PMID: 19232131Schoenian I, Spiteller M, Ghaste M, Wirth R, Herz H, & Spiteller D (2011). Chemical basis of the synergism and antagonism in microbial communities in the nests of leaf-cutting ants. Proceedings of the National Academy of Sciences of the United States of America, 108 (5), 1955-60 PMID: 21245311---Follow me on Twitter!
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Wilson AC, Ashton PD, Calevro F, Charles H, Colella S, Febvay G, Jander G, Kushlan PF, Macdonald SJ, Schwartz JF.... (2010) Genomic insight into the amino acid relations of the pea aphid, Acyrthosiphon pisum, with its symbiotic bacterium Buchnera aphidicola. Insect molecular biology, 249-58. PMID: 20482655
Thomas GH, Zucker J, Macdonald SJ, Sorokin A, Goryanin I, & Douglas AE. (2009) A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola. BMC systems biology, 24. PMID: 19232131
Schoenian I, Spiteller M, Ghaste M, Wirth R, Herz H, & Spiteller D. (2011) Chemical basis of the synergism and antagonism in microbial communities in the nests of leaf-cutting ants. Proceedings of the National Academy of Sciences of the United States of America, 108(5), 1955-60. PMID: 21245311
Neisseria meningitidis is a bacteria which lives in the throats of around 30% of the human population. In most cases it causes no problems at all and just exists as a normal part of the throat microbial flora. In some patients however it can start to colonise the bloodstream and brain, leading to cases of septicemia and meningitis which are highly dangerous and can be fatal.The invasion starts with individual bacteria, which adhere to the epithelial cells that cover the inside of the throat. They then start to divide and proliferate to form large aggregated colonies. Within these colonies they are connected to each other, and to the epithelial cells, by protrusions from the bacterial cell surface called pili which are shown below for a wild-type (i.e un-genetically modified) Neisseria meningitidis:Image taken from the reference below. The arrow points to one of the pili, and the insert shows a close-up of it.These pili are often modified by the attachment of small molecules to the pili proteins, including the molecule phosphoglycerol (shown on the right for those interested in structure). To test the effects of the addition of phosphoglycerol, the researchers found which gene caused the addition of this molecule onto the pili (the pptB gene), and removed it from the cell. Without the pptB gene there was still the same number of pili around the cell, but they were not clumping together as much. Instead of the thick fibres seen in the wild type above (caused by large bundles of pili) only little stringy fibres were seen. These thin spindly fibres show that without the addition of phosphoglycerol, the pili cannot clump together.This is important medically as Type IV pili bundle formation and N. meningitidis aggregation for infection are linked. Interestingly it was not the aggregation that was affected by removing the phosphoglyerol but the ability of individual bacteria to leave the aggregate to infect other parts of the body. In wild-type bacteria, the pptB gene is strongly activated only after several rounds of division within the aggregate, so it looks like the addition of phosphoglycerol acts as a switch, communicating to the bacteria that enough of them have aggregated and it is now time to leave. If the pptB is activated due to large numbers of bacteria it could act as a communication of the population density - signalling to the individual bacteria that the current location is far too crowded, and it has better chances of survival if it leaves.---Chamot-Rooke J, Mikaty G, Malosse C, Soyer M, Dumont A, Gault J, Imhaus AF, Martin P, Trellet M, Clary G, Chafey P, Camoin L, Nilges M, Nassif X, & Duménil G (2011). Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science (New York, N.Y.), 331 (6018), 778-82 PMID: 21311024---Follow me on Twitter!
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Chamot-Rooke J, Mikaty G, Malosse C, Soyer M, Dumont A, Gault J, Imhaus AF, Martin P, Trellet M, Clary G.... (2011) Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science (New York, N.Y.), 331(6018), 778-82. PMID: 21311024
I like studying bacteria. I find them fascinating, wonderful little creatures, able to do as much (and often more!) with a single cell as other organisms need whole multicellular bodies to achieve. I like exploring the places bacteria live, the things they can do, the ways they manage to exploit practically every niche on earth, and of course most importantly how I can exploit them.But not everyone loves bacteria, and at heart I am a biochemist which means, among other things, that I get to teach younger biochemists. This means I do occasionally find myself venturing uncertainly into the world of the multicellular and while doing so recently I found an interesting paper on cell signalling (reference below) which I thought I would share.All cells need to be able to communicate, but while bacteria know that everyone they communicate with is a competitor, multicellular organisms have cells that need to be able to cooperate in a strange and slightly twisted form of cellular-communism. Each cell needs to know when it can divide (usualy never), when to grow, when to release chemicals and, ultimatly,when to sacrifice itself for the Greater Good.Cellular communication is mostly a chemical affair, with small molecules called ligands being sent from one cell to another and recognised by receptors on the cell surface. These receptors can take many forms, but one of the more common ones is the form of a seven-transmembrane spanning receptor, so called because it goes through the membrane seven times:Picture (c)me and my dodgy art skills. The protein is in blue, the membrane in pink, and the ligand bound on the outer cell surface is the red blob.Binding of a ligand causes a conformational change in the whole structure, most importantly in that long intracellular tail shown above. This can then activate other molecules inside the cell, with the end result that a specific gene is turned on or off. In the classical model of this process the intracellular tail interacted with a little molecule called the G protein which carried the message through to the genome. Another protein that featured in this model was B-arrestin, which was thought to desensitise the receptor and the G-protein by re-setting it back to its original state, i.e switching the thing off. This model is shown below:Picture (c) me. This is a simplified diagram, in 'reality' there are a lot more different proteins involved, but these are the main ones, and the important ones for this paper.New evidence is coming to light which modifies this model. Firstly, it's been found that the B-arrestin does more than just switch off the G-protein, it is also capible of sending its own signals, through a cascade of different proteins. Both the G protein and the B-arrestin can be used to pass on the message sent by the ligand. Secondly, it's been found that these two proteins are not activated equally, a bias can be displayed, sending the signal through one of these two intermediate proteins; either the G protein, or the B-agonist or a mixture of the two. This bias can be either due to the properties of the receptor, or those of the ligand binding to it. Experimentally you can generate a bias by altering either the receptor or the ligand to prefer binding to the B-agonist, and you can plot these on mathematical-looking graphs.You can tell this is a biology graph because there are no actual numbers, just vague concepts :p (c) me.The actual physiological effects of this are only starting to be explored, as it introduces an extra level of complexity to intracellular control. The use of several different ligands, all with varying degrees of bias at the same receptor, could produce more subtle cellular output responses. Within a multicellular organism, the better your intracellular communication is, the more likely your organism is to grow happily and survive.---Rajagopal S, Rajagopal K, & Lefkowitz RJ (2010). Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nature reviews. Drug discovery, 9 (5), 373-86 PMID: 20431569---Follow me on Twitter!
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Rajagopal S, Rajagopal K, & Lefkowitz RJ. (2010) Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nature reviews. Drug discovery, 9(5), 373-86. PMID: 20431569
Antibiotics are effective against bacteria because they target and knock out specific functions that are vital for bacterial survival. As most bacterial infections involve rapid growth and division of the invading bacteria, many commercial antibiotics currently target metabolically active cells, by blocking enzymes needed for growth, reproduction, or cell wall synthesis. While these will kill acute bacterial infections they are often far less effective against dormant bacteria in longer-term persistent infections.Rather than targeting metabolic enzymes, the current strategies being explored to combat dormant bacteria target either the membrane, or membrane bound proteins. Both of these approaches destabilise the bacterial membrane and help to break the cell apart and can act against processes such as energy synthesis which occur in both active and dormant cells.a=targeting important metabolic proteins in the membrane. b=targeting the actual cell-membrane. Picture is copywrite me :pIn eukaryotic cells, such as the cells of plants and animals, the enzymes that create energy for the cell are kept safely hidden away in specialised intracellular compartments, such as mitochondria. As energy production requires an ion gradient across a membrane, these compartments all have sets of internal membranes. Bacteria however do not have this luxury, and instead have all their metabolic enzymes in the outer cell membrane, as this is the only membrane they have. Inhibitors of energy metabolism can therefore bind directly to target enzymes in the membrane involved in the production of energy. This can be highly effective against cells whose interior is hard to get into, such as Mycobacterium tuberculosis which lurks inside tuberculosis granulomas. Even in the absence of growth, cells still require a minimal energy input to survive, so blocking off these enzymes kills both dormant and active cells.Drug developed to help combat TB by attacking cell membrane metabolic enzymes. This drug is currently in stage three clinical trials.The membrane-targeting drugs act directly on the lipid bilayer that surrounds the bacterial cell, breaking it up and destroying the bacterial cellular integrity. Although human cells are also surrounded by lipid bilayers they have fewer negatively charged phosopholipids and also contain cholesterol (not present in bacterial membranes) allowing membrane-targeted drugs to be specific for human pathogens rather than killing surrounding human cells. The drugs that are used to attack the cell wall can vary hugely in size and structure but they all share one common property; they are highly lipophilic (i.e they are attracted to lipids). This allows them to interact with the cell membrane and break it apart.Lipophilic drug capible of targeting bacterial cell membranesThere’s something about those molecular diagrams of drugs that I love. I think it’s my biochemical background. I’m never totally happy with a schematic until I can see how the chemicals are interacting on a molecular scale.As well as being useful against dormant bacteria these new antimicrobials show promise as strategies for dealing with arising antibiotic resistance. Bacteria can evolve to cope with as many challenges as are thrown at them, but hopefully it should take them a little longer learn to survive entirely without a cell wall…Although there are some that can do that already.---Hurdle JG, O'Neill AJ, Chopra I, & Lee RE (2011). Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nature reviews. Microbiology, 9 (1), 62-75 PMID: 21164535---Follow me on Twitter!
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Hurdle JG, O'Neill AJ, Chopra I, & Lee RE. (2011) Targeting bacterial membrane function: an underexploited mechanism for treating persistent infections. Nature reviews. Microbiology, 9(1), 62-75. PMID: 21164535
Eukaryotes - animals, plants, and other creatures with a nucleus, evolve relatively slowely. Genetic variation occurs through changes in the DNA between generations; each offspring will be a genetic product of their parents and nothing else. Genetic changes happen down the generations. In bacteria, however, everything is a little more insane. Because bacteria can change DNA with almost any other bacteria they come accross, there is less of a conserved genetic record. Genes are flying around all over the place which can make it very difficult to seperate bacteria into neat taxonomic groups.It's helped by the fact that bacterial genomes aren't completely random, and can usually be seperated into 'core' genes and 'accessory' genes. Core genes are most useful to taxonomists as they show what the bacterial species actually is, and where it sits within molecular phylogeny. The accessory genes are more interesting to bacteriologists as the play a more significant role in phenotypic differences and determin what the bacteria do. Paradoxically, the accessory genes are also the ones used most in adaption (think of antibiotic resistance) and are therefore more likely to be evolutionarily selected for or against. These accessory genes are often found in specific 'hypervariable' regions of the genome called genomic islands.Cartoon by Nick Kim, www.nearingzero.netThe increase in second-generation sequencing technologies opened up the ability for large scale comparitive-genomics studies; essentially sequencing huge numbers of bacterial genomes and then comparing them all to each other. Back in the day, population studies were done using an approach known as MultiLocus Sequence Typing (MLST) - which took seven core genes and sequenced those for each bacteria. Nowadays you can sequences all the parts of the genome you need in hundreds of different strains.As with most new microbiology technologies, these new techniques are initially being applied to human pathogens, as human pathogen research is (rightly) where most of the money is. Using wholescale sequencing technologies on pathogens such as Clostridium difficile which has high levels of antibiotic resistance. The grand aim is to try and understand both the extent and the distribution of natural genomic variation between one bacterial species. This could help to understand what roles are played by bacterial migrations, recombinations (switching DNA around), active selection and drift in the spread of antibiotic resistance.C. difficile is a very genetically diverse species which has been evolving for the last 1.8 million years. As each bacteria is likely to replicate at least once a day, this allows for a huge amount of change and genetic variation. It might be suspected that the virulent species is formed from a single offshoot, one bacteria that became virulent and then passed that ability onto its offspring but instead it looks like virulence arose in many different lineages, most likely through horizontal gene transfer. This means that each different virulent strain is likely to show a relatively large amount of variation in the rest of its genome.It isn't just small bits of DNA on separate plasmids that C. difficile can exchange, they can also carry out homologous recombination, a process by which whole sections of the bacterial genome can be cut out and shared between related species. This process is aided by the presence of 'mobile elements' within the genome, i.e pieces of DNA which are particularly good at jumping around and splicing themselves in and out of bacterial chromosomes. It turns out that the C. difficile genome contains lots of mobile elements.From a bacteriologists point of view this is a fascinating example of just how variable a single strain of bacterial species can be. From a medical viewpoint it's more worrying. The ability of highly virulent bacteria to chop out large portions of their genome and pass them onto other, potentially non-virulent strains could help to spread not just antibiotic resistance, but also other tricks like biofilm formation and different enzymes which help the bacteria to cope with antibiotic challenges.Not only that but it means that every gene in the genome has been tried and tested by many different strains in many different conditions. They aren't just good genes for the bacteria to be hanging onto. They're the best.---He, M., Sebaihia, M., Lawley, T., Stabler, R., Dawson, L., Martin, M., Holt, K., Seth-Smith, H., Quail, M., Rance, R., Brooks, K., Churcher, C., Harris, D., Bentley, S., Burrows, C., Clark, L., Corton, C., Murray, V., Rose, G., Thurston, S., van Tonder, A., Walker, D., Wren, B., Dougan, G., & Parkhill, J. (2010). Evolutionary dynamics of Clostridium difficile over short and long time scales Proceedings of the National Academy of Sciences, 107 (16), 7527-7532 DOI: 10.1073/pnas.0914322107... Read more »
He, M., Sebaihia, M., Lawley, T., Stabler, R., Dawson, L., Martin, M., Holt, K., Seth-Smith, H., Quail, M., Rance, R.... (2010) Evolutionary dynamics of Clostridium difficile over short and long time scales. Proceedings of the National Academy of Sciences, 107(16), 7527-7532. DOI: 10.1073/pnas.0914322107
This guest post comes from my fiancé who is a Psychiatrist. I've been very excited about this post for a while, because unlike me, he is a published author who has written a book on Consciousness and the philosophy of mind.Microbes and MadnessAt first glance, it would be reasonable to assume that my profession and that of the author of this fabulous blog are poles apart. However, everything in nature has a connection, and so it is not surprising to discover a fascinating area where psychiatry and bacteriology overlap.A broad range of pathogens are known to cause psychiatric sequelae, including worms (neurocysticercosis), protozoa (cerebral malaria, toxoplasmosis), viruses (HIV, herpes simplex encephalitis, rabies), prions (Creutzfeldt-Jakob disease, kuru), and, of course, bacteria (neurosyphilis, Lyme disease, post-streptococcal syndromes). However, in the spirit of this blog, this post will be focusing on bacteria.There are essentially four mechanisms through which bacteria cause psychiatric symptoms in humans: I. Bacteria can infect the central nervous system and cause direct damage to brain cells. II. Bacteria can trigger a powerful systemic inflammatory response that results in a disruption in brain function. III. Bacteria can trigger an adaptive immune response which produces antibodies that cross-react with host central nervous system proteins. IV. Bacteria can be the objects of a phobia.Syphilis and Lyme disease are examples of infections which involve the first mechanism. Syphilis is caused by spirochaetes of the species Treponema pallidum, and is sexually-transmitted. Lyme disease is caused by spirochaetes of the genus Borrelia, and is vector-borne, with ticks from the genus Ixodes being the commonest vector. Both diseases are associated with widespread dissemination of infection of multiple organ systems, and are notorious for their protean manifestations.The range of possible psychiatric presentations is vast. Syphilis, in particular, can mimic any psychiatric syndrome, and was a common diagnosis in psychiatric inpatients a century ago. The possible range of presentations include delirium, dementia, psychosis, mania, and personality changes. Lesions of the frontal lobes are associated with personality changes and disinhibited behaviour, whereas those of the temporal and parietal lobes are associated with cognitive decline. Lyme disease can also mimic several different psychiatric syndromes, but typically affects the limbic system, causing disorders of emotional regulation, including panic attacks, phobias, depression, and obsessive-compulsive behaviour.The second mechanism listed refers to sepsis-associated delirium. No human organ system is a closed system, including the central nervous system. Bacterial infections with a focus outside the outside the brain are capable of causing a systemic reaction, which affects the brain. The result is an acute confusional state, or delirium.Common causes are pneumonias and urinary tract infections, although infections of other organ systems are also frequently implicated. Delirium presents as a transient global disorder of cognition. Typically, there is clouding of awareness, disorientation, impaired attention, fluctuating alertness with agitation or drowsiness, hallucinations, illusion, and vague delusions. The state is thought to be caused by a global disruption of brain function, which may result from the effects of a systemic inflammatory response to infection. These effects may include systemic vasodilation causing cerebral hypoperfusion, increased permeability of capillaries allowing toxins to cross the blood-brain barrier, the action of inflammatory cytokines on the brain, and increased body temperature resulting in an increase in neuronal oxygen demand.The third mechanism is seen following infections with group A beta-haemolytic Streptococcus pyogenes, such as scarlet fever and tonsillitis. In response to infection, the adaptive immune system produces antibodies against antigens on the invading pathogen. However, some streptococcal antigens are similar in some way to antigens on host tissues, and so the antibodies produced mistakenly recognise and attack the host tissues. Examples of post-streptococcal autoimmune diseases include rheumatic fever, glomerulnephritis, and Sydenham’s chorea.A psychiatric syndrome caused by this mechanism is PANDAS, which stands for paediatric autoimmune neuropsychiatric disorder associated with streptococcus. This typically presents as a dramatic onset of obsessive-compulsive disorder, tic disorders, or Gilles de la Tourette syndrome following an infection with group A beta-haemolytic Streptococcus pyogenes in childhood. It is thought to be a result of autoimmune damage to the basal ganglia, which is the part of the brain involved with the initiation and regulation of motor commands. Interestingly, it has also been suggested that encephalitis lethargica, a mysterious syndrome which caused an epidemic during World War I, may also be caused by a post-streptococcal autoimmune reaction.The fourth and final mechanism listed refers to mysophobia, or the pathological fear of germs. Behavioural symptoms include repeated washing of hands, excessive cleanliness, and avoidance of social contact. Anxiety and panic attacks also occur. Although the behavioural manifestations are similar, mysophobia is not to be confused with obsessive-compulsive disorder. The former is a phobic disorder, in which the fear of germs underlies the behaviour, and the function of the behaviour is avoidance of the phobic object. In the latter, the behaviour is compulsively carried out in response to the obsession that the behaviour must be carried out.I hope to have provided an comprehensive overview of some of the interesting ways microbes can cause mental and behavioural disturbances in humans. The function of this ability is open to speculation. The film 28 Days Later tells the story of an artificial ‘Rage’ virus. When a human is infected, he or she becomes uncontrollably aggressive, attacking other humans and infecting them with viruses in the process. Thus, the viruses’ effect on human behaviour is clearly advantageous to their spread and propagation. However, outside of fiction, the advantages of pathogens’ effects on human behaviour is less obvious. Even with rabies, on which the symptoms of the ‘Rage’ were based, there has been no documented human-to-human transmission through bites. In fact, the only documented cases of human-to-human transmission of rabies were of transplant recipients receiving corneas from infected donors! It is therefore not known what evolutionary advantage, if any, the psychiatric sequelae of infection convey to the pathogens. It is possible that they are epiphenomenal.---Pfister D, Siegemund M, Dell-Kuster S, Smielewski P, Rüegg S, Strebel SP, Marsch SC, Pargger H, & Steiner LA (2008). Cerebral perfusion in sepsis-associated delirium. Critical care (London, England), 12 (3) PMID: 18457586Neurosyphilis: Considerations For A Psychiatrist Mark A. Ritchie, Joseph A. Perdigao, Mark A. RitchieThe Neuropsychiatric Assessment of Lyme DiseaseA. Mazzola, G. Mazzola (2006). OCD And Beta Haemolytic Streptococcus: A Nasty Association. Priory publishing link... Read more »
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