Are Professional Medication Practices Giving Drug Resistance a Head Start?

New research done at Penn State has started to question the medication strategy generally accepted by health professionals. This strategy generally includes aggressive use of medications in order to kill all pathogens. This approach has been so broadly accepted for so long that it has not been questioned as it should.

Professor Andrew Read is the led professor on the research done at Penn State. Read is a professor of biology and entomology at Penn State as well as the director of the Center for Infectious Disease Dynamics at the university. His research has brought up a new idea that the orthodox approach of aggressive medication may not actually be the best way to combat drug-resistant diseases but on the contrary may actually be promoting the expansion of these bacteria.

The process of a bacteria becoming resistant to a drug is a matter of evolution. Read uses malaria in Africa as a example for the aggressive use of a medication and the eventual resistance to that drug. Chloroquine was the drug of choice again malaria in Africa but is now useless because mutant parasites have formed that are resistant to the drug and continue to cause malaria. When these aggressive drug therapies are used all drug-sensitive parasites are being eliminated which in turn actually gives the drug-resistant parasites less competition and a better shot of actually infecting the body. Another example used is the bacterium MRSA that is known to be drug-resistant and a great enemy of hospitals in their fight to prevent and treat it.

Read's thought is that if these aggressive drugs are used more sparingly and with less aggression in order to allow the bodies immune system to catch up and do it's job. A lot of the time the immune system is just overwhelmed so by using these drugs more sparingly it can help eliminate enough of the pathogens that the immune system can actually eliminate the drug-resistant pathogens.

This more cautious approach of drug therapy will also help keep medications effective longer by delaying the formation of resistant strains of bacteria. The research by Read and everyone involved at Penn State is only the beginning to research that has the potential to change the protocol used for medicating patients. This research will help medical professionals find strategies for drug use that will keep drugs effective longer and help patients prevent, fight, and defeat many infectious diseases.

Sources:

Penn State. "Current strategy for medicating patients may be giving many drug-resistant diseases a big competitive advantage."ScienceDaily, 23 Jun. 2011. Web. 26 Jun. 2011. http://www.sciencedaily.com/releases/2011/06/110622125803.htm

Read, Andrew F., Troy Day, and Silvie Huijben. "The Evolution of Drug Resistance and the Curious Orthodoxy of Aggressive Chemotherapy." Proceedings of the National Academy of Sciences. National Academy of Sciences, 20 June 2011. Web. 26 June 2011. http://www.pnas.org/content/early/2011/06/20/1100299108.

Dbellovibrio to Absorb Biofilms

Surfaces are important in the establishment of microbial communities. For example, water and ions can adhere to the surface of soil particles, creating a nutrient rich microenvironment. Microbes establish themselves in microenvironments, forming communities called biofilms. Biofilms form almost anywhere there is a surface and some water. For instance, you grow your own biofilm on your teeth every night! Biofilms form when certain types of bacteria settle on surfaces and begin to produce sticky polysaccharides. Development continues as other microbes colonize the surface or become trapped in the polysaccharide, establishing the biofilm community. Microbes that live in biofilms are protected from drying out and from antimicrobials. This can make organisms that live in biofilms difficult to kill which is why they cause a wide variety of infections. In the lungs of a cystic fibrosis patient, Pseudomonas aeruginosa forms a biofilm community that is resistant to antibiotics. Biofilms also play a role in urinary tract infections, middle ear infections, and forms on catheters. In hospital settings, biofilm communities can be difficult to remove from ventilation systems and other moist areas. However, new research on the genus Bdellovibrio may lead to medical breakthroughs.

Bdellovibrio is known as a vampire in the bacterial world because they attack, destroy, and insert themselves into their gram-negative prey. It is aerobic, has curved rods, and is propelled by single flagella. Bdellovibrio has a complex life cycle, but only require one to three hours for completion. The bacterium swims rapidly about 100 cell lengths per second until it collides with its prey. It attaches to the bacterium’s surface and begins to rotate at great speed to create a hole in the host cell wall. Bdellovibrio enters leaving its flagella behind. After entry, Bdellovibrio grows between the cell wall and plasma membrane. The host bacterium forms a circular shape called a bdelloplast. Bdellovibrio elongates as it digests the host’s cytoplasm. The host cell is lysed and motile Bdellovibrio that were reproduced are released.

Carey Lambert and Andy Fenton, from the University of Nottingham, UK, who conducted this research found that Bdellovibrio can switch “engines” and crawl at 20 cell lengths. This allows “Bdellovibrio to exit from a bacterial prey cell which it has finished digesting and crawl across a solid surface to find other bacterial prey to invade.” They predict in environments with too little liquid that Bdellovibrio could be used to kill pathogenic bacteria on solid surfaces. Also, Myxobacteria have been identified to have similar slow engines like Bdellovibrio which could lead to medical advances. Myxobacteria are also gram-negative, aerobic cells and they glide along solid surfaces, feeding and leaving a slime trail. Most are predators of other microbes. A mass of myxobacteria can digest their prey more easily because they produce more enzymes than an individual cell. They secrete lytic enzymes and antibiotics to kill their prey. However, unlike Bdellovibrio they can grow in absence of prey. In conclusion, Bdellovibrio has an ability to attack and remove surface-attached bacteria or biofilms. It is hoped that Bdellovibrio species in slow motion can prey on or “mop up” bacteria in biofilms. These predators could reduce the bacterial population and change the structure of the biofilm community.

Sources:
American Society for Microbiology (2011, June 20) Could bacterial predator be harnessed to mop up biofilms? ScienceDaily. Retrieved June 25, 2011, from http://www.sciencedaily.com/releases/2011/06/110617184857.htm

Fester, R. (2011). E-z microbiology. NY: Barrons Educational Series Inc.

Nunez, M.E. Biophysics of bacterial biofilms [Web log message]. Retrieved from http://www.mtholyoke.edu/~menunez/ResearchPage/AFM.html

A New Way to Fight Malaria

There may be a new combatant in the fight against malaria. Scientists from Johns Hopkins University Bloomberg School of Public Health and Malaria Research Institute have discovered a symbiotic bacteria living in the midgut of some mosquitos that inhibits the growth of the malaria parasite. In tests, the Enterobacter bacterium strain known as Esp. Z was shown to have the ability to kill 99% of the malaria causing parasites.

The world health implications of this discovery are huge. Malaria kills nearly 800,000 people a year. In 2008, there were 247 million cases of malaria and nearly one million deaths – mostly among children living in Africa. In Africa a child dies every 45 seconds of Malaria where the disease accounts for 20% of all childhood deaths.

The human malaria parasite Plasmodium falciparum enters the mosquito when it feeds off an infected human. In the mosquito’s midgut the parasite encounters many obstacles to its development including human blood-derived factors, the mosquitos’ own innate immune responses, and resident microbiota. Although most of the parasites are killed in the mosquito it only takes the survival of a small number to continue the cycle of transmission back to humans.

Dr. George Dimopoulos and his colleagues conducted their research using bacteria isolated from Anopheles arabiensis populations of wild mosquitoes collected in southern Zambia. They discovered that the way that the Plasmodium parasite is destroyed by the Esp. Z bacteria is a rather roundabout mechanism that may lead to longstanding and effective preventative measures against the disease. The Esp. Z bacteria does not directly attack the malaria parasite. Because of this it does not produce an immune response from the parasite and therefore is left alone to continue its deadly (to the parasite) and beneficial (to humans) work. The researchers found the secret to its effectiveness in a byproduct produced by the microbe during its replication. Reactive oxygen species (known as free radicals) produced by the Esp. Z bacteria were discovered to inhibit the development of the Plasmodium parasite. Dependant on the concentration of the Esp. Z present, up to 99% of the parasites failed to mature in the mosquito’s midgut. To verify that these free radicals were indeed the cause of the death of the parasites, antioxidants were supplemented with the bacteria in cultures. In cultures where vitamin C was added the parasites continued normal development even in the presence of reactive oxygen species producing Esp. Z.. And again in cultures where another potent antioxidant, reduced glutathione, was added with the Esp. Z, development occured on a normal basis. In cultures where Esp. Z was absent the addition of vitamin C had no affect on the parasite numbers, indicating that the the free radicals were causing the death of the parasite.

Although this study was conducted with Esp. Z isolated from a single collection of mosquitoes in Zambia made during one rainy season, 25% of the insects collected harbored the strain. The results may have long reaching effects. The question begs, “Might it be possible to increase the populations of Esp_Z or other naturally inhibitory bacteria by manipulating the makeup of the midgut microbial flora in wild mosquitoes as a way to control malaria worldwide by stopping the disease before it starts?”

Sources:

http://myhealthbowl.com/latest-health-news/a-bacterium-living-in-the-gut-of-mosquito-itself-is-able-to-kill-malarial-parasite/

http://www.who.int/mediacentre/factsheets/fs094/en/index.html

http://www.who.int/malaria/world_malaria_report_2010/worldmalariareport2010.pdf

http://www.sciencemag.org.ezproxy.vccs.edu:2048/content/332/6031/855.full

http://www.microscopy-uk.org.uk/mag//imgdec03/wd2/filtros0001.jpg

Bacteria Found in Soil Shown to Decrease Anxiety and Improve Learning Capabilities

Many people take pleasure in spending time outdoors, whether it be hiking, biking, gardening, or simply enjoying a day at the park. Not only do these outside activities provide an opportunity for fresh air, sunshine, and fun, but studies have shown that spending time outdoors and having contact with the soil can decrease anxiety and possibly improve learning capabilities.

Myobacterium vaccae is a species of bacteria that is a part of the mycobacterium genus. These cells are straight or slightly curved rods, and they are usually considered Gram positive. M. vaccae is a nonpathogenic bacterium that naturally lives in the soil. Immunotherapy for allergic asthma, cancer, depression, leprosy, psoriasis, dermatitis, eczema, and tuberculosis are all areas of research that have been pursued regarding a M. vaccae vaccine.

Research has shown that M. vaccae stimulates the generation of serotonin and norepinephrine in the brain. According to past studies linked to these findings, scientists have concluded that M. vaccae shows a decrease in anxiety. In addition, a more recent study proposed that neuron growth was stimulated when heat-killed M. vaccae was injected into mice.

Dorothy Matthews and Susan Jenks of The Sage Colleges in Troy, New York conducted some research. Matthews expressed that individuals are likely to breathe in the natural soil bacterium, Myobacterium vaccae, while spending time outdoors. She also stated, “Since serotonin plays a role in learning, we wondered if live M. vaccae could improve learning in mice.” This curiosity led Matthews and Jenks to conduct an experiment that involved feeding live bacteria to mice and then assessing their ability to navigate a maze. After performing the experiment, they concluded that the mice that were fed the live M. vaccae did, in fact, navigate the maze twice as fast and with less anxiety as the control mice that were not fed the live bacterium. Matthews and Jenks then performed two subsequent experiments that involved withholding the bacterium from the M. vaccae fed mice. The scientists found that the mice still navigated the maze slightly faster than the control mice. However, the effect did not last long, which meant that the effect was a direct result of the presence of the bacterium. Matthews said that this research proposes that M. vaccae may be linked to learning in mammals. She stated that “it is interesting to speculate that creating learning environments in schools that include time in the outdoors where M. vaccae is present may decrease anxiety and improve the ability to learn new tasks.”

If Myobacterium vaccae does, in fact, have the same effects on humans, it would be necessary to spend time outdoors on a regular basis in order to stay in contact with the bacterium. Nonetheless, the information and conclusions gathered from these studies give even more reason to enjoy the great outdoors.

Sources:

American Society for Microbiology. "Can bacteria make you smarter?." ScienceDaily, 25 May 2010. Web. 24 Jun. 2011.
http://en.wikipedia.org/wiki/Mycobacterium
http://en.wikipedia.org/wiki/Mycobacterium_vaccae
http://www.physorg.com/news193928997.html
http://www.good.is/post/breathing-soil-bacteria-makes-you-smarter/

The Rapid Spread of the Vaccinia Virus

The Rapid Spread of the Vaccinia Virus

It is known that the Vaccinia virus produces one batch of viral particles every five to six hours. The Vaccinia virus however, can spread over vast areas of uninfected cells at a rate of 1.2 cells per hour (Smith 2011). This infection rate is far faster than seems possible; but new research is now providing an explanation for this microscopic mystery.

Image: Vaccinia virus infecting host cell.

“This 'viral bouncing' accounts for experiments in which Vaccinia spreads much more quickly across a dish of cells than viral reproduction rates should allow,” says Geoffrey Smith of Imperial College London (Vastag 2010). So how is it that a virus is able to spread so rapidly? Geoffrey Smith and his team, at Imperial College London have discovered an answer to this question. Using live imaging of fluorescently tagged viruses, Smith noticed that the virus was actually tricking the cell into blasting its particles out large distances to new uninfected cells. At the same time the virus tags the infected cell as “infected” and thus signaling to other virus particles to move to another location. This sort of smart-bomb system is what has allowed the Vaccinia virus to spread great distances quickly (Vastag 2010).

Viral Launch Pads

Smith and his team utilized a specific strand of the Vaccinia virus. One that expresses the green florescent protein that shows up later in infection. Smith then had an easy identification signal that told him when a cell was infected (Smith 2011) (the cell would turn green). The Vaccinia virus would then enter a cell and infect its nucleus; exchanging its genetic information with the host cell’s. The virus then immediately turns on transcription and translation to produce two viral proteins known as A33 and A36 (Smith 2011). Other studies have shown that these proteins are escorted to the cell membrane by microtubules and microfilaments. When the proteins reach the membrane they diffuse through it and then rest on the outside of the cell in viral protein complexes (Vastag 2010). When a new viral particle comes in contact with this complex it initiates the creation of an actin arm that pushes the particles up, up, and away to infect another healthy host cell. With this new information Smith and his team went about crippling the A33 and A36 protein genes in the Vaccinia virus which resulted in the dramatic slowing of infection rates (Smith 2011). These two proteins however, were found to be fairly insufficient; as it takes the presence of both proteins simultaneously to initiate an actin projection from the cell membrane. If only one protein was present the viral particles would not bond to the protein complex and thus no propulsion would be executed (Smith 2011).

This spreading process is vital for a virus in its ability to survive. Though this process is not good for humans who contract these viruses, as Smith says “it is Darwinian,” and all things have equal right to survival (Smith 2011). This understanding of the Vaccinia virus is making scientist look closer at all viruses for this type of expansion mechanism. The Vaccinia virus its self is not harmful, but it closely mimics the small pox virus and has been used as a live vaccine for small pox in the past. These studies of the Vaccinia virus are very important milestones in the combat of all deadly diseases.

References

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Smith, G.L. (2011). A mechanism for rapid virus spread. SGM Microbiology Today, 90-94. Retrieved from http://www.sgm.ac.uk/pubs/micro_today/pdf/051102.pdf

Vastag, B. (2010, January 21). Virus spreads by bouncing off infected cells. Nature News, 1, Retrieved from http://www.nature.com/news/2010/100121/full/news.2010.26.html

Malaria Vaccine

       Malaria is a disease where a protozoan parasite from an infected mosquito, invades the body’s red blood cells. The parasite transfers from an infected mosquito to a human through the skin and then goes to the liver cells where it replicates itself so the parasite can enter the blood and bursts red blood cells (shown in the picture). Under a microscope, the parasite looks spherical, yellow, and1/20^th the size of a red blood cell. There are four different species of the malaria parasite with the most common being Plasmodium falciparum being the most aggressive and deadly. Some forms cause recurring infections but rarely kills. Most often malaria begins with a fever and can kill a person within 24 hours or continue a fever and chills cycle for many days. 

It is a public health problem today in more than 100 countries and causes more than one million deaths a year. It is more prominent in third world countries with mostly children and pregnant women dying, but can occur everywhere. This disparity is caused by lack of proper funding and clean potable water for the communities, this furthermore leads to the root of the problem with tangent water. They use anti-malarial drugs to combat the disease once a person obtains it, but over time the malarial parasites have developed resistance to theses drugs. Recently a new study shows they may have found a way to discover a vaccination.

            Scientists have many theories on the development of a vaccine for malaria. One is to generate T-cells against liver-stage antigens to disrupt the parasitic life style. Some scientists have generated a genetically attenuated parasite (GAP) that can stop the protozoan parasite from replicating in the late liver stage. Before scientists were just trying to stop replication in the early live stage but this doesn’t stop all of the sporozoites from replicating. So now they are trying genetically attenuated parasites, which are produced from targeted gene deletions, to stop late liver stage developments. They have succeeded with mice and are hoping to further their studies. So hopefully this new strategy will lead to the vaccination for this horrible disease. Dr. Kappe and Dr. Harty now need a powerful model to find new parasite protein-based vaccine candidates that protect against infection in the liver and blood.

            A lot of past research acknowledges the fact that the vaccination is tricky since this parasite can be resistant to the dosage. They still believe that “vaccinations with viral-based vaccines hold promise for the prevention of malaria,” but they all seem to be on trials with animals. However, this is progress with this new strategy, and the way modern medicine continues on its path, the cure is likely in the near future. Which is hopeful since malaria has become more resistant and people get few immunities from catching this parasite, so incidents have increased globally.
 

Sources
Malaria Vaccination Strategy
MalariaFoundation
ELSEVIER

Ice-Nucleating Bacteria Poses New Possibilities

For approximately twenty years ski resorts and the like have used artificial snow to ensure good snow coverage at low altitudes and to lengthen the ski season. A very interesting microorganism, Pseudomonas syringae, is a biological additive that plays a role in keeping snow on the slopes. Pseudomonas syringae is capable of "making" snow because it contains ice-nucleating proteins on its cell surface. The protein binds water molecules together in a pattern similar to an ice crystal's lattice. This protein allows for ice to form at warmer temperatures than is normal.

Pseudomonas syringae is a rod shaped gram negative pathogen that is found naturally in the atmosphere. The bacterium has been found in hail, snow, and rain. The ice-nucleating protein found in Pseudomonas syringae, if found in clouds, could indicate that the proteins evolved as part of the bacterial life cycle. Thus, it is speculated that the bacterium uses the protein on its cell surface to facilitate its own precipitation in an effort to return to the ground. This is logical because, although some nutrients exist in the atmosphere, P. syringae is a pathogen that affects plants. The atmosphere is not an ideal environment for the bacterium to live in. On the ground, this bacterium is infectious to a wide variety of plant species. Its ability to freeze water at fairly high temperatures is very harmful to plants and causes frost damage to plant surfaces. This breakdown of epithelial tissue allows the bacteria to gain access to the plant's nutrients. Also, it is speculated that the diverse array of effectors, toxins, and hormones produced by this pathogen play an important role in manipulating plant metabolism to promote infection.

Although toxic to plants, Pseudomonas syringae is not pathogenic to humans. Studies conducted did however reveal that extreme exposure to the bacterium (such as workers creating the artificial snow) does pose certain health risks. Normal exposure to the endotoxins found in the artificial snow is no different than the exposure to the endotoxins found in naturally occurring snow.

The existence of P. syringae in snow and rainfall has led scientists to hypothesize that the bacterium also helps to create rain clouds. If this is true, Pseudomonas syringae may have the ability to play an even greater role than the making of artificial snow. While Pseudomonas syringae is harmful to crops, a new breakthrough may be "raining down" in the future that will allow the bacterium to be viewed differently. The ability to create rain clouds from a bacterium would drastically change pre-existing environments and could have a global effect. The idea is that the bacterium can be used to create rain clouds in areas that experience drought. Farmers who live in temperatures that do no fall low enough for frost to form could grow bacteria harboring plants. Ideally, the bacteria would disperse into the atmosphere and create rainclouds. The change from making snow, to making clouds is an extreme leap, but if successful the environmental impact of one little microorganism could alter life for many places in the world.

Sources:

Hooper, R. "Bacteria Make Snow and Rain Fall." New Scientist 197.2646 (2008): 14. Web. 19 Jun 2011.

Lagriffoul, A., J.L. Boudenne, R. Absi, J.J. Ballet, and J.M. Berfeaud, "Bacterial-based additives for the production of artificial snow: What are the risks to human health?." Science of the Total Environment 408.7 (2010): 1659-1666

Rico, A., S.L. McCraw, and G.M. Preston. "The metabolic interface between Pseudomonas syringae and plant cells." Current Opinion in Microbiology. 14.1 (2011): 31-38. Web. 19 Jun 2011.

Science Friday. N.p., 27052011. Web. 19 Jun 2011. http://www.sciencefriday.com/program/archives/201105271.

E. coli, the Endless Possibilities

From food poisoning to medicine and everything in between, these bacteria seem almost like the eighth wonder of the world. When it comes to Escherichia coli (E. coli), the sky is the limit. Known to many as the main cause of food poisoning, this bacterium is anything but a pestilence to most, at least to scientist or those interested in the race to find the answer to the current fuel crisis. With gas prices skyrocketing and the uncertainty of the economy, everything is worth a shot when it comes to lowering the cost of the biggest punch in the American’s wallet, gas. So why look at bacteria that are known to be ruthless? It’s easy, a new fuel source. According to Desmond Lun, an associate professor of computer science at Rutgers University-Camden, “E. coli has been used as a lab organism for more than 60 years and it's well-studied. We know a lot about its genetics and how to manipulate it.” This has been relatively helpful to scientists over the past couple of years. With 60 plus years of knowledge it seems like a no brainer to study this microorganism. One of the basic functions of bacteria is to keep reproducing in order to survive. Bacteria are asexual, so in order to reproduce, bacteria undergo cell division, or binary fission. This means that bacteria clone themselves and in doing so share the same DNA as each other. Since bacteria do this, it is very easy to spawn millions of the same bacteria in just days, this is why looking to bacteria, or more specifically E. coli, to aid in the production of possible alternate fuel sources is of great interest to those who want to study it. This allows for a massive amount of biofuel to potentially be produced by a bacterium so well known, studied, and common. Now, why choose E. coli out of all the bacteria in the world? According to George Church at Harvard Medical School, “E. coli tolerated the genetic changes quite well…[it] grows fast, three times faster than yeast, 50 times faster than Mycoplasma, 100 times faster than most agricultural microbes...it can survive in detergents or gasoline that will kill lesser creatures, like us. It's fairly easily manipulated…[p]lus, E. coli can be turned into a microbial factory for almost anything that is presently manufactured but organic—from electrical conductors to fuel.” Why not invest money into something scientists can “play God” with? As Lun said, "It's widely acknowledged that making fuel out of food sources is not very sustainable. It's too expensive and it competes with our food sources." Shouldn’t we first give thought into a potentially remarkable fuel source like E. coli or even bacteria first instead of competing with the current food supply? These types of bacteria grow anywhere conceivable and do not interfere with consumable products. For those who manage to get past its ruthless behavior and who are interested in studying this foul bacterium, nothing but good will be gained from it, and not just to those who study this alternative fuel source, but the world as well.

Sources:

http://www.scientificamerican.com/article.cfm?id=bacteria-transformed-into-biofuel-refineries

http://www.sciencedaily.com/releases/2010/09/100903104828.htm