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The idea of the blog was to provide accurate and interesting information and reflections on science from somebody currently in the field.
Lab Rat
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The model for bacterial death by antibiotics was fairly simply until recently. Antibiotics work by targeting a certain area of the bacteria; beta-lactams target the cell wall, Rifamycins target RNA synthesis, tetracyclins inhibit protein synthesis etc. The theory was that by inhibiting these processes, a certain vital function within the bacteria would be stopped, leading to its death.However due to research done by Kohanski (references below) the story is looking a bit more complicated. Looking........ Read more »
Kohanski MA, Dwyer DJ, Hayete B, Lawrence CA, & Collins JJ. (2007) A common mechanism of cellular death induced by bactericidal antibiotics. Cell, 130(5), 797-810. PMID: 17803904
Kohanski MA, Dwyer DJ, & Collins JJ. (2010) How antibiotics kill bacteria: from targets to networks. Nature reviews. Microbiology, 8(6), 423-35. PMID: 20440275
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......... Read more »
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 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 so........ Read more »
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
DNA is one of the most important components of the cell. In eukaryote cells (i.e the cells of humans and plants) it is stored inside a nucleus that keeps it safe and away from dangerous things like free radicals produced by the metabolic reactions of the cell. In bacterial cells the DNA isn't nearly as well protected, but the main bulk of the bacterial chromosome (excluding the little floating plasmids) is all kept together in a bundle usually referred to as a nucleoid. However the DNA in cells ........ Read more »
Schröder O, & Wagner R. (2002) The bacterial regulatory protein H-NS--a versatile modulator of nucleic acid structures. Biological chemistry, 383(6), 945-60. PMID: 12222684
I while ago I wrote a post about how virus's get from the outside of the cell to the interior of the nucleus and found that virus particles are able to hitchhike on the cells internal transport systems. I was quite interested therefore to find a paper in Nature Reviews (reference below) that revealed that not only do virus's latch on to host proteins to travel around inside the cell, they also use host extracellular processes for travelling around the body. And outside the cell it's not just vir........ Read more »
Salinas S, Schiavo G, & Kremer EJ. (2010) A hitchhiker's guide to the nervous system: the complex journey of viruses and toxins. Nature reviews. Microbiology, 8(9), 645-55. PMID: 20706281
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. Th........ Read more »
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
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........ Read more »
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
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 teac........ Read more »
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
Methods of bacterial predation, including a short exploration of the 'hunting' behaviour seen in Myxococcus xanthus.... Read more »
Berleman JE, & Kirby JR. (2009) Deciphering the hunting strategy of a bacterial wolfpack. FEMS microbiology reviews, 33(5), 942-57. PMID: 19519767
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........ Read more »
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
This is the first post of my SGM conference series: I'm going to try and write about seven topics from the Society for General Microbiology September conference over the course of two weeks. The first topic I'm looking at is Protein Folding and Misfolding which consisted of thirteen presentations covering various aspects of protein folding in bacteria, fungi and yeast. As a quick background: when proteins are synthesized they are constructed as long chains of amino-acids which then need to fold........ Read more »
Knowles TJ, Scott-Tucker A, Overduin M, & Henderson IR. (2009) Membrane protein architects: the role of the BAM complex in outer membrane protein assembly. Nature reviews. Microbiology, 7(3), 206-14. PMID: 19182809
Johnson, A., & Jensen, R. (2004) Barreling through the membrane. Nature Structural , 11(2), 113-114. DOI: 10.1038/nsmb0204-113
Even in the world of the very small, there are significant differences in size. A eukaryote cell (i.e a human cell) for example is relatively big, in microscopic terms. Most other things that interact with the cell at the microscopic level, are far smaller than it, such as bateria, viruses and signalling molecules.A virus isn't much more than a small capsule of proteins with a little bit of DNA inside. Once it gets inside a eukaryote cell, it's very much in the position of a small child wanderin........ Read more »
Kerstin Radtke, Daniela Kieneke, André Wolfstein, Kathrin Michael, Walter Steffen, Tim Scholz, Axel Karger, Beate Sodeik. (2010) Plus- and Minus-End Directed Microtubule Motors Bind Simultaneously to Herpes Simplex Virus Capsids Using Different Inner Tegument Structures. PLoS Patholgens, 6(7). info:/e1000991
Exploring work done on L-form baacilis subtilis (without cell walls) and how this provides clues to how early life might have grown and propagated.... Read more »
Leaver, M., Domínguez-Cuevas, P., Coxhead, J., Daniel, R., & Errington, J. (2009) Life without a wall or division machine in Bacillus subtilis. Nature, 460(7254), 538-538. DOI: 10.1038/nature08232
Zhu TF, & Szostak JW. (2009) Coupled Growth and Division of Model Protocell Membranes. Journal of the American Chemical Society. PMID: 19323552
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 t........ 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
Durrant, W., & Dong, X. (2004) SYSTEMIC ACQUIRED RESISTANCE. Annual Review of Phytopathology, 42(1), 185-209. DOI: 10.1146/annurev.phyto.42.040803.140421
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
MRSA, the antibiotic resistant form of Staphylococcus aureus is a major problem in hospitals. The antibiotic resistance makes it hard to erradicate, not just from patients, but in the surounding environment, on surfaces, on medical equipment, on the walls of the hospital. In order to minimise the numbers of dangerous bacteria found in hospital surroundings, quite a lot of research has gone into creating antibacterial coverings or coatings that would reduce the number of bacteria p. Currently how........ Read more »
Pangule RC, Brooks SJ, Dinu CZ, Bale SS, Salmon SL, Zhu G, Metzger DW, Kane RS, & Dordick JS. (2010) Antistaphylococcal nanocomposite films based on enzyme-nanotube conjugates. ACS nano, 4(7), 3993-4000. PMID: 20604574
The response of Strep. ceolicolor to cell-wall attacking antibiotics.... Read more »
Hutchings, M., Hong, H., Leibovitz, E., Sutcliffe, I., & Buttner, M. (2006) The E Cell Envelope Stress Response of Streptomyces coelicolor Is Influenced by a Novel Lipoprotein, CseA. Journal of Bacteriology, 188(20), 7222-7229. DOI: 10.1128/JB.00818-06
Hong, H., Paget, M., & Buttner, M. (2002) A signal transduction system in Streptomyces coelicolor that activates the expression of a putative cell wall glycan operon in response to vancomycin and other cell wall-specific antibiotics. Molecular Microbiology, 44(5), 1199-1211. DOI: 10.1046/j.1365-2958.2002.02960.x
Jacobs C, Frère JM, & Normark S. (1997) Cytosolic intermediates for cell wall biosynthesis and degradation control inducible beta-lactam resistance in gram-negative bacteria. Cell, 88(6), 823-32. PMID: 9118225
I haven't worked very much with bacteria that infect humans. Most of my lab work has been done in the fields of either synthetic biology (which works with model organisms) or antibiotic production, which works on soil bacteria that produce the antibiotics. Human bacterial parasites therefore hold the fascination of the slightly exotic, not least because they sometimes do things like this:Figure from"Molecular Biology of the Cell, Fourth Edition"by Alberts et al.I've written before about some of ........ Read more »
Ray K, Marteyn B, Sansonetti PJ, & Tang CM. (2009) Life on the inside: the intracellular lifestyle of cytosolic bacteria. Nature reviews. Microbiology, 7(5), 333-40. PMID: 19369949
Kuo SC, & McGrath JL. (2000) Steps and fluctuations of Listeria monocytogenes during actin-based motility. Nature, 407(6807), 1026-9. PMID: 11069185
I've written about biofilms a couple of times before but it's an interesting enough topic to keep returning to. As a brief summery, biofilms are large collected colonies of bacteria, often surrounded by a sticky mesh of glycoproteins. They are ultra-annoying in the case of infectious bacteria as the bacteria deep in the depths of the biofilm will not be exposed to any antibiotics, the layers of glycoprotein and surrounding bacteria will protect them.Although living within a biofilm contains sig........ Read more »
Berne C, Kysela DT, & Brun YV. (2010) A bacterial extracellular DNA inhibits settling of motile progeny cells within a biofilm. Molecular microbiology. PMID: 20598083
Jermy A. (2010) eDNA limits biofilm attachment. Nature reviews. Microbiology, 8(9), 612. PMID: 20737663
Most places which contain bacteria tend to contain lots of them. In the environment (i.e outside human bodies) bacteria often live in large colonies which can make it difficult to explore their reactions to changing conditions. In the lab, with just one bacteria, information about responses can be obtained by transcriptomics; looking at how the transcriptome changes as the environment does.The transcriptome is the set of all the mRNA within the cell. Unlike the genome, which is the all DNA prese........ Read more »
Gilbert JA, Field D, Huang Y, Edwards R, Li W, Gilna P, & Joint I. (2008) Detection of large numbers of novel sequences in the metatranscriptomes of complex marine microbial communities. PloS one, 3(8). PMID: 18725995
Over at Thoughtomics, Lucas has a post up about the evolution of mitochondrial import systems. He starts by going back in time two billion years:"Life was well underway at the time, with proto-bacteria already populating the oceans for over hundreds of millions of years. One of the cells alive at the time, swallowed an alpha-proteobacterium. Something remarkable happened: the alpha-proteobacterium did not die but survived in the host cell. Over time, the host and symbiont became to be dependent ........ Read more »
Gross J, & Bhattacharya D. (2009) Revaluating the evolution of the Toc and Tic protein translocons. Trends in plant science, 14(1), 13-20. PMID: 19042148
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