Bacterium Protects Against Asthma

            New studies from Germany suggest infection from the bacterium, Helicobacter pylori, offers protection against allergy-induced asthma. But in industrial societies this bacterium has disappeared from the human body because of the hygiene hypothesis. The hygiene hypothesis says “that modern hygiene measures have led to a lack of exposure to infectious agents, which is important for the normal maturation of the immune system.” Since the bacterium isn’t in the body, allergic diseases are increasing from the air pollution.

            Asthma is a chronic inflammatory disease of the airways, which can cause “wheezing, breathlessness, chest tightness and coughing.” It’s estimated that “ 6.8 million U.S. children have asthma.” People think asthma contributes to obesity; both are the two leading public health problems in the U.S. Allergy induced asthma occurs when then the body’s immune system falsely identifies a non-threatening substance, such as pollen or pollution, as a harmful intruder into the body. This causes a reaction from the human body in which the antibodies in your immune system attempt to attack the foreign substance. This is seen when the body produces

excessive amounts of mucus discharge, or what most people experience when battling allergies, but it can also lead to the lungs and airways being affected. When these are affected it can trigger asthmatic episodes and this causes allergy-induced asthma.

Helicobacter pylori infect half the world’s population and are resistant to gastric acid. It can cause different stomach problems or diseases but most have no symptoms and therefore killed off with antibiotics as a precaution.  The researchers at the University of Zurich and University Medical Center of the Johannes Gutenberg believe that early infection with the H. pylori bacterium will protect against asthma and other allergic diseases. They have tested their theory on mice and the mice that didn’t have the bacteria had weaker defenses in adulthood. In industrial areas asthma is linked to “the widespread use of antibiotics and the subsequent disappearance of microorganisms” in the human body.

But Helicobacter pylori can be a dangerous bacterium, even though the majority is harmless to the human body. Bacterial, host and environmental factors determines each individual disease risk. Helicobacter pylori usually colonize the body during childhood and can persist lifelong if left untreated and the various stomach diseases will occur during adulthood.  The most important H. pylori associated illnesses are duodenal and gastric ulceration, as well as inflammation of different parts of the stomach or intestines. Picture shown of H. pylori is shown below.

Since in industrial societies we kill the bacterium with antibiotics and then expose ourselves to pollution and smoke we need “to develop preventative and therapeutic strategies” to help combat asthma now that we understand a little bit more about it. 



Gastric Bacterium Helicobacter Pylori Protects Against Asthma
The inflammatory and immune response to Helicobacter pylori infection
Obesity and Asthma: A Dangerous Link in Children: An Integrative Review of the Literature

Universal Flu Vaccine A Step Closer

Annually changing flu vaccines may soon lead to a single, universal flu vaccine according to a new report from scientists at The Scripps research Institute and the Dutch biopharmaceutical company Crucell. They explain an antibody tested on animals, that can prevent and possibly cure infections within a broad spectrum of influenza viruses, including some seasonal and potentially pandemic strains.

The finding shows the influenza subtypes neutralized with the new antibody include H3N2, which killed an estimated 1 million people in Asia in the late 1960s. This antibody, and the one reported in 2009 have the potential to protect people against most influenza viruses.

Ian Wilson, the Hansen Professor of Structural Biology and a member of the Skaggs Institute for Chemical Biology at Scripps Research, has been working with Crucell scientists to help overcome the problem with current influenza vaccines, which is that they work only against the fe strains that the vaccine makers predict will dominate in a given year, making their effectiveness temporary. In addition, current influenza vaccines provide little or no protection against unforeseen strains.

These problems reflect a basic flu-virus defense mechanism. The viruses come packaged in spherical or filamentous envelopes that are studded with mushroom-shaped hemagglutinin (HA) proteins. These outer structures effectively serve as decoys for a normal antibody response. The outer loops on the HA head seem to attract most of the antibodies, but in a certain strain these loops can mutate to evade an antibody response within months. Antiviral drugs aimed at these and other viral targets also lose effectiveness as flu virus populations evolve. The goal of the research is to find and attack relatively consistent and functionally important structures on flu viruses.

By sifting through the blood of people who have been immunized with flu vaccines, researchers discovered an antibody that bound to one such exposed structure. In mice, an injection of the antibody could prevent or even cure a lethal infection by about half of flu viruses, including H1 viruses such as H1N1, which caused deadly global pandemics in 1918 and 2009.

Researchers determined the 3D molecular structure of CR6261 and its binding site on HA. The binding site turned out to be on HA’s lower, less-reachable stalk portion. The bind of CR6261 to that region interferes with flu viruses’ ability to deliver their genetic material into host cells and start a new infection.

Crucell researchers searched for an antibody that could neutralize some of the remaining flu viruses unaffected by CR6261, and recently found one called CR8020. CR8020 powerfully neutralizes a range of human-affected flu viruses in lab-dish tests and in mice. The affected viruses include H3 and H7, which have already caused pandemic or sporadic human infections.

Crucell is about to begin initial clinical trials of CR6261 in human volunteers, and the company expects to begin similar trials of CR8020. If those trials succeed, the two antibodies could be combined and used in a passive immunotherapy approach. This would mainly be useful as a fast acting therapy against epidemic or pandemic influenza viruses. The ultimate goal is an active vaccine.

Sources:

http://www.telegraph.co.uk/health/healthnews/8625929/Universal-flu-vaccine-a-step-closer.html

http://www.telegraph.co.uk/health/healthnews/8625929/Universal-flu-vaccine-a-step-closer.html

http://www.sciencemag.org/content/early/2011/07/06/science.1204839.abstract

Discoveries in Mitochondria Open New Field of Cancer Research

A whole new field of epigenetics research from Virginia Common Wealth University Massey Cancer Center has been discovered with the possibility of developing future gene therapies to treat cancer as well as other age-associated diseases. Epigenetics refers to the process that controls which genes get expressed in the nucleus of a cell, ultimately determining that cell's biological characteristics.

Shirley M. Taylor, Ph.D., researcher at VCU Massey Cancer Center and associate professor in the VCU Department of Microbiology and Immunology at VCU School of Medicine, was a graduate student when her research helped establish the field of epigenetics. Many years later Dr. Taylor and her colleagues have expanded their knowledge from understanding enzymes are in existence not only in the nuclei but also in the mitochondria.

All of an organism's hereditary information exists in two distinct genomes of all mammal's cells. Taylor's study found two DNA modifications in the mitochondrial genome. From the article, "In diseases such as cancer, epigenetic control is lost," says Taylor. "Genes that should be switched on are switched off and vice versa, leading to uncontrolled growth. Our research indicates that errors in gene expression could be unfolding in mitochondria, possibly contributing to loss of mitochondrial function typical of cancer and a host of other age-related diseases." One of the main areas of focus for Taylor and her team is trying to determine whether epigenetic control is a factor contributing to defects that lead to serious illnesses. Understanding the impact drugs have on gene expression in the nucleus and discovering beneficial ways of using it for the mitochondria would be huge.

It is always interesting to me when new studies and discoveries come out about steps taken towards cancer research. Cancer affects millions of people worldwide every year and is the world's leading cause of death. According to the World Health Organization, "Deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030." Although the cure for cancer or other serious age related diseases may not be discovered shortly, it still gives hope that new research in the field of Microbiology is taking strides toward making that a reality one day!

References

Virginia Commonwealth University (2011, June 21). Discoveries in mitochondria open new field of cancer research. ScienceDaily. Retrieved July 3, 2011, from http://www.sciencedaily.com­ /releases/2011/06/110620161306.htm

L. S. Shock, P. V. Thakkar, E. J. Peterson, R. G. Moran, S. M. Taylor. DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria. Proceedings of the National Academy of Sciences, 2011; 108 (9): 3630

http://www.who.int/cancer/en/

Natural-Occurring Cavity Fighters: Streptococcus Salivarius

The mouth has over 700 different species of bacteria living in it, some of which are harmful and others that are actually beneficial for the host. Plaque, the cause of cavities, is made by the formation of biofilms. Those bacteria that produce the biofilms causing plaque are called Streptococcus Mutans. “S. mutans digests sugars and produces acids that can eat into enamel and cause cavities (Science Magazine).” Streptococcus salivarius are other bacteria commonly found in the oral cavity, however, these bacteria are beneficial. These bacteria quickly take up residence in the mouth after a day of life or so and they mostly live on the tongue. Streptococcus salivarius is a spherical, gram-positive bacteria. The S. salivarius bacteria is an opportunistic pathogen, which means it is harmless to those with a healthy immune system, but when the immune system becomes compromised it can become harmful. Just recently in 2009, these bacteria were discovered to help play a part in prevention of plaque formation by secreting an enzyme that breaks down the buildup of Streptococcus mutan bioflim.

Hidenobu Senpuku, a scientist in Tokyo, wanted to see which enzyme in S. salivarius breaks down plaque. Using chromatography, he separated out the different proteins from the bacteria. He found that the enzyme, FruA, inhibited the growth of S. mutans cells the most. This is probably because this enzyme is used in the S. salivarius bacteria to break down complex sugars.

Researchers then found that another form of the enzyme, FruA, is also produced by a fungus. Aspergillus niger is a common fungus that produces FruA, but has a slightly different amino acid sequence than the S. salvarius FruA, but it still contains plaque fighting abilities. The discovery of FruA in the Aspergillus niger fungus could make the possibility of toothpaste containing the enzyme, FruA, available in the near future. It would still be very difficult to create a toothpaste with a perfect balance that would allow the enzyme to stay in tack and be able to function once used.

So does the fact that humans produce natural plaque reducers mean that we can stop brushing our teeth as often? Unfortunately, no it doesn’t. Researchers found that the enzyme will stop working if overloaded with sugars. It won’t be able to fight of the formation of biofilms which can cause cavities.

The more scientists find out about the S. Salivarius bacterium, the better. “A better knowledge of the molecular and physiologic factors which allow it to colonize dental plaque and to interact with other species will help in designing strategies for the prevention of cavities, especially in children (Genoscope).”

Resources:

http://news.sciencemag.org/sciencenow/2011/04/a-bacterium-that-acts-like-a-toothbrush.html

http://www.genoscope.cns.fr/spip/Streptococcus-salivarius,483.html

http://aem.asm.org/cgi/content/full/77/5/1572

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