Archive for February, 2009

Microbial survival in challenging environments

Friday, February 6th, 2009

Hydrothermal vent Extreme environments, such as deep-sea hydrothermal vents 2,500 meters below the ocean surface, support large macrofaunal communities via microbially mediated carbon fixation processes using chemicals (chemoautotrophy) rather than light (photoautotrophy). Photosynthesis cannot occur in this dark environment, where hot, toxic fluids oozing from below the seafloor combine with cold seawater at very high pressures.

Nautilia profundicola, distantly related to the pathogenic Helicobacter and Campylobacter species, contains a number of genes and pathways predicted to be important in DNA repair, environmental sensing, and metabolism, which are novel to either its subdivision or to all microbes. The study combined genome analysis with physiological and ecological observations to investigate the importance of one gene in N. profundicola. Previous studies found the gene only in microorganisms growing in temperatures greater than 80oC, but N. profundicola thrives best at much lower temperatures.

The genes and deduced metabolic pathways include several hydrogen uptake and release systems as well as a novel predicted nitrogen assimilation pathway. One gene involved in DNA repair, reverse gyrase, was thought to be a hallmark protein in hyperthermophiles, which are microbes that grow above 80oC. The gene’s presence in N. profundicola suggests that it might play a role in the bacterium’s ability to survive rapid and frequent temperature fluctuations in its environment. The researchers also uncovered further adaptations to the vent environment, including genes necessary for growth and sensing environmental conditions, and a new route for nitrate assimilation related to how other bacteria use ammonia as an energy source. These results help to explain how microbes survive near deep-sea hydrothermal vents, where conditions are thought to resemble those found on early Earth, as described in the study. Improved understanding of microbes living in these conditions may aid our understanding of how life evolved here.

Adaptations to Submarine Hydrothermal Environments Exemplified by the Genome of Nautilia profundicola. 2009 PLoS Genet 5(2): e1000362
Submarine hydrothermal vents are model systems for the Archaean Earth environment, and some sites maintain conditions that may have favored the formation and evolution of cellular life. Vents are typified by rapid fluctuations in temperature and redox potential that impose a strong selective pressure on resident microbial communities. Nautilia profundicola strain Am-H is a moderately thermophilic, deeply-branching Epsilonproteobacterium found free-living at hydrothermal vents and is a member of the microbial mass on the dorsal surface of vent polychaete, Alvinella pompejana. Analysis of the 1.7-Mbp genome of N. profundicola uncovered adaptations to the vent environment – some unique and some shared with other Epsilonproteobacterial genomes. The major findings included: (1) a diverse suite of hydrogenases coupled to a relatively simple electron transport chain, (2) numerous stress response systems, (3) a novel predicted nitrate assimilation pathway with hydroxylamine as a key intermediate, and (4) a gene (rgy) encoding the hallmark protein for hyperthermophilic growth, reverse gyrase. Additional experiments indicated that expression of rgy in strain Am-H was induced over 100-fold with a 20oC increase above the optimal growth temperature of this bacterium and that closely related rgy genes are present and expressed in bacterial communities residing in geographically distinct thermophilic environments. N. profundicola, therefore, is a model Epsilonproteobacterium that contains all the genes necessary for life in the extreme conditions widely believed to reflect those in the Archaean biosphere – anaerobic, sulfur, H2- and CO2-rich, with fluctuating redox potentials and temperatures. In addition, reverse gyrase appears to be an important and common adaptation for mesophiles and moderate thermophiles that inhabit ecological niches characterized by rapid and frequent temperature fluctuations and, as such, can no longer be considered a unique feature of hyperthermophiles.

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The Pathogenicity of Pandemic Influenza Viruses

Thursday, February 5th, 2009

Dr. Peter Palese describes how reconstructing the extinct 1918 pandemic influenza virus by reverse genetics can help us better understand molecular basis of virulence and the mechanisms by which pandemic influenza viruses are transmitted.

Germ Warfare

Wednesday, February 4th, 2009

Pneumococcus A surprising example of interspecies competition is the production by certain bacteria of hydrogen peroxide at concentrations that are lethal for others. A case in point is the displacement of Staphylococcus aureus by Streptococcus pneumoniae in the nasopharynx, which is of considerable clinical significance. How it is accomplished, however, has been a great mystery, because H2O2 is a very well known disinfectant whose lethality is largely due to the production of hyperoxides through the abiological Fenton reaction. In this report, we have solved the mystery by showing that H2O2 at the concentrations typically produced by pneumococci kills lysogenic but not nonlysogenic staphylococci by inducing the SOS response. The SOS response, a stress response to DNA damage, not only invokes DNA repair mechanisms but also induces resident prophages, and the resulting lysis is responsible for H2O2 lethality. Because the vast majority of S. aureus strains are lysogenic, the production of H2O2 is a very widely effective antistaphylococcal strategy. Pneumococci, however, which are also commonly lysogenic and undergo SOS induction in response to DNA-damaging agents such as mitomycin C, are not SOS-induced on exposure to H2O2. This is apparently because they are resistant to the DNA-damaging effects of the Fenton reaction. The production of an SOS-inducing signal to activate prophages in neighboring organisms is thus a rather unique competitive strategy, which we suggest may be in widespread use for bacterial interference. However, this strategy has as a by-product the release of active phage, which can potentially spread mobile genetic elements carrying virulence genes.

Killing niche competitors by remote-control bacteriophage induction. PNAS USA January 13, 2009

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Cytomegalovirus immune manipulation

Tuesday, February 3rd, 2009

HCMV No one likes to feel like they have been manipulated, but in the case of cytomegalovirus (CMV) immune manipulation, we do not really have much choice. Whether you call it CMV immune modulation, manipulation, or evasion, the bottom line is that CMV alters the immune response in such a way to allow the establishment of latency with lifelong shedding. With millions of years of coevolution within their hosts, CMVs, like other herpesviruses, encode numerous proteins that can broadly influence the magnitude and quality of both innate and adaptive immune responses. These viral proteins include both homologues of host proteins, such as MHC class I or chemokine homologues, and proteins with little similarity to any other known proteins, such as the chemokine binding protein. Although a strong immune response is launched against CMV, these virally encoded proteins can interfere with the host’s ability to efficiently recognize and clear virus, while others induce or alter specific immune responses to benefit viral replication or spread within the host. Modulation of host immunity allows survival of both the virus and the host. One way of describing it would be a kind of “mutually assured survival” (as opposed to MAD, Mutually Assured Destruction). Evaluation of this relationship provides important insights into the life cycle of CMV as well as a greater understanding of the complexity of the immune response to pathogens in general.

Feeling manipulated: cytomegalovirus immune manipulation. 2009 Virology Journal 2009, 6: 4

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Slip Sliding Away

Monday, February 2nd, 2009


When fish school, birds flock, insects and bacteria swarm, a population of similar individuals cruises along similar, sometimes cyclic, paths. How do the members of a swarm anticipate the movement of others to coordinate movement with them? And how do members, when each is moving rapidly near to others, avoid impeding their neighbor’s motion? These general issues, which have yet to be resolved for any schooling, flocking, or swarming organism, can be investigated in swarming bacteria. Such investigation might have practical value because swarming enables pathogens like Proteus, for example, to invade the urinary tract and to spread along the surface of catheters placed in the urethra. The behavior of swarming individuals might also suggest ways to speed high density automobile or pedestrian traffic and ways to avoid traffic jams. Bacterial sensory systems and behaviors are more amenable to analysis than those of animals. Because they are relatively small; several thousand bacteria can be followed in a time lapse movie of a swarm. Among bacteria that swarm are the hyperflagellated bacteria, all of the Myxobacteria, which lack flagella, and the Bacteriodetes that include Cytophaga, Flavobacteria, and Bacteriodes. Millions of Myxococcus xanthus cells are found to swarm outward for more than a week at a steady rate of approximately 0.1 mm/hr, a rate close to half the speed of individual cell movement. Swarming gives them a significant growth advantage: Whereas cells in the swarmcenter are competing with each other for nutrient and oxygen, cells at the swarm edge have practically unfettered access to both.

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Periodic reversal of direction allows Myxobacteria to swarm. PNAS USA January 21, 2009

Many bacteria can rapidly traverse surfaces from which they are extracting nutrient for growth. They generate flat, spreading colonies, called swarms because they resemble swarms of insects. We seek to understand how members of any dense swarm spread efficiently while being able to perceive and interfere minimally with the motion of others. To this end, we investigate swarms of the myxobacterium, Myxococcus xanthus. Individual M. xanthus cells are elongated; they always move in the direction of their long axis; and they are in constant motion, repeatedly touching each other. Remarkably, they regularly reverse their gliding directions. We have constructed a detailed cell- and behavior-based computational model of M. xanthus swarming that allows the organization of cells to be computed. By using the model, we are able to show that reversals of gliding direction are essential for swarming and that reversals increase the outflow of cells across the edge of the swarm. Cells at the swarm edge gain maximum exposure to nutrient and oxygen. We also find that the reversal period predicted to maximize the outflow of cells is the same (within the errors of measurement) as the period observed in experiments with normal M. xanthus cells. This coincidence suggests that the circuit regulating reversals evolved to its current sensitivity under selection for growth achieved by swarming. Finally, we observe that, with time, reversals increase the cell alignment, and generate clusters of parallel cells.

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