Saturday, May 13, 2006
Why Ganga Water is sacred for Hindus
Bacteria resistant to most or all available antibiotics are causing increasingly serious problems, raising widespread fears of returning to a pre-antibiotic era of untreatable infections and epidemics. Despite intensive work by drug companies, no new classes of antibiotics have been found in the last 30 years. The emergence of these antibiotic-resistant bacterial strains has forced researchers to explore alternative antibacterial therapies, such as the ability of bacterial viruses (bacteriophages) to treat bacterial infections.This activity destroyed cholera bacteria in culture. M.E. Hankin demonstrated that it could pass through fine porcelain filters and was destroyed by boiling. He suggested that this activity might be responsible for restricting the cholera outbreak among the people that consumed the river water. At the beginning of the 20th century, Frederick Twort from England, and Felix d'Herelle from Canada, working at the Pasteur Institute in Paris, reported isolating similar filterable entities capable of destroying bacterial cultures. It was d'Herelle who named these ultra microbes, "Bacteriophages" (bacteria eaters) and pioneered the use of phages for treating Shigella dysentery in rural France. When d'Herelle was asked to investigate the outbreak of dysentery, which was afflicting soldiers engaged in fighting World War I, he quickly found that the dysentery was caused by the bacteria called Shigella. He cultured the bacteria to study their growth and noticed that sometimes, clear areas could be seen on plates of bacteria. He recognized the significance of the clear areas (plaques). He realized that something was killing the bacteria and he wondered if he could use whatever it was as a treatment to cure the dysentery. So, d'Herelle started monitoring an individual patient carefully. Each day, he took samples of the man's feces and filtered them through a porcelain filter to remove any bacteria. He mixed samples of filtrate with bacterial cells and spread them on agar plates. Initially he saw nothing but on the fourth day he started to see plaques. He now performed a direct test, he recovered the material from a plaque and mixed it with a flask containing a growing culture of bacteria. The next morning he noticed that the culture which the night before had been very turbid with the presence of bacteria, was now perfectly clear. There exist two classifications of bacteriophages: lytic and lysogenic. All references to bacteriophages for therapeutic uses are to lytic bacteriophages (lysogenic bacteriophages are not useful for therapeutic purposes). T4 bacteriophage is an assembly of protein components and DNA. The head is protein membrane, shaped like a kind of prolate icosahedron with 30 facets and filled with viral DNA or RNA. It is attached by a collar (and neck) to a tail consisting of hollow core surrounded by a contractile sheath and based on a spiked end plate to which six fibers are attached. The spikes and fibers affix the phage to a bacterial surface, by binding to specific receptors. The sheath contracts, driving the core through the bacterial cell wall, and the phage injects its nucleic acid (DNA or RNA) into the bacterium. The bacteriophage DNA redirects the bacterial cell's biosynthetic machinery to produce hundreds of new bacteriophages which, when released, destroy the bacterial cell. The newly produced bacteriophages invade other bacteria in the vicinity and the process is repeated about every thirty minutes until all of the bacteria are eliminated. At this time, the bacteriophages, being non-living entities, self-eliminate because the bacteria that they require as hosts no longer exist.Felix d'Herelle was highly successful in treating dysentery in rural France, cholera in India and later cured diseases like typhoid fever, bubonic plague, wound infections, avian typhosis and hemorrhagic septicemia of the buffalo using phage therapy, where as other early attempts to treat infections with phage gave mixed results. At the time that nature of bacteriophages was not clearly known and in the 1940’s, further research into the use of bacteriophages to treat bacterial infections was stopped in the United States. However, research into the antibacterial use of bacteriophages still continued in the former Soviet Union, with some success in treating bacterial infections. Only recently, has this technology again gained popularity in the United States, due to emergence of many antibiotic-resistant strains of bacteria. Bacteriophage therapy has many advantages over antibiotics. Bacteriophages are highly specific, where as antibiotics kill all bacteria without specificity, beneficial bacteria (e.g. in the intestinal tract) that perform crucial functions for the human body are also affected by antibiotics and harmful pathogens can then grow more easily. Secondary infections like the Pseudomonas species or Clostridium dificile develop in this way and cause severe diarrhea and colon infections. Bacteriophages can specifically target the harmful bacterium, eliminate it, and leave the beneficial bacteria intact. Bacteriophages cannot cause disease to humans, animals, or plants; they can only cause harm to bacteria. Furthermore, for almost all known bacterial species there exists one or more bacteriophages specific to that species Due to bacteriophage's exponential rate of self-replication, usually a small dose is sufficient for curing a bacterial infection. Bacteriophages can penetrate deep into an infection and destroy all of the particular bacterium growing there. Antibiotics, on the other hand, often encounter difficulty penetrating deep bacterial infections and delivery of the antibiotic to all of the bacteria then becomes a significant obstacle. This obstacle rarely exists in the case of bacteriophages. In addition to being self-replicating, bacteriophages are also self-limiting. When all of the bacteria are infected with bacteriophages, their numbers start to decline and the number of bacteriophages also decreases. Bacteriophages require their specific bacterium in order to exist and, in the absence of that specific bacterium, they are eliminated rapidly. Bacteriophage preparations are highly stable and can be dispersed in any media, they can be stored for long periods, and have a low cost of production.The bacteriophage therapy is currently being used to treat post-burn bacterial infections, which are a major problem for those recovering from the trauma of third-degree burns. Within 24 hours, burn patients can start suffering from opportunistic bacterial attacks. As an alternative to treating post-burn bacterial infections by antibiotics, bacteriophages have been in use in certain parts of the world, such as at Tbilisi in Georgia and in Poland, and this approach has now been more widely recognized. Results have shown that bacteriophage therapy has an 80% success rate against Enterococcus infections and up to 90% against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Pseudomonas aeruginosa is the most common post-burn infection, and it is known to be notoriously resistant to a variety of antibiotics. For the most effective treatment of post-burn infections, a cocktail of bacteriophages is sprayed at the site of burns, this will reduce the chance of the bacteria developing resistance against the different bacteriophages. Bacteriophage solutions or aerosols can also be used to treat the surfaces and instruments in operating rooms as well as the skin of the surgical patient (prior to surgery).In addition to treating human illnesses, bacterio-phage are being used to treat illnesses in livestock. A bacteriophage which is highly active and rapidly lytic in vitro and which attaches to the K1 capsule antigens of bacteremic strains of E. coli has been very effective in preventing and treating septicemia and cerebritis or meningitis in chickens. The bacteriophage treatment was shown to be more effective than multiple doses of antibiotic. Bacteriophages were found in all tissues examined (muscle, blood, spleen, liver, and brain) within 5 minutes of their injection into the muscle. Experiments were conducted to see if this therapy would cure calves, which were suffering from diarrhoea caused by toxin-producing E. coli. Calves that responded to bacteriophage treatment had lower numbers of the bacteria in their gastrointestinal tracts and continued to excrete bacteriophage until all of the toxic E. coli had disappeared. Another practical use of bacteriophages is for bacterial identification through a process called phage typing, which is the use of patterns of sensitivity to a specific battery of bacteriophages to precisely identify microbial strains. This technique takes advantage of the fine specificity of many bacteriophages for their hosts and is still in common use around the world. Enzymes from bacteriophages have also been isolated and shown antibacterial qualities. One such enzyme is PlyG, which is a type of bacteriophage lysin. The lysins, produced by the bacteriophage, translocate from the bacterial cytoplasm into the cell-wall matrix, where they rapidly hydrolyze covalent bonds essential for peptidoglycan integrity, causing bacterial lysis and concomitant release of progeny bacteriophages. PlyG is produced by the bacteriophage gamma, which infects Bacillus anthracis, the bacterium that causes anthrax. Isolated PlyG has been shown to kill B. anthracis in vitro and in vivo. The spores of B. anthracis are resistant to PlyG-induced lysis. However, the spores can be triggered to germinate by adding a solution of L-alanine to them; once they germinate PlyG in the same solution can cause lysis. The lytic specificity of PlyG has also been exploited as part of a rapid method for the identification of B. anthracis .The sophisticated ability of bacteriophages to destroy their bacterial hosts can also have a very negative commercial impact; phage contaminants occasionally spread havoc and financial disaster for the various fermentation industries that depend on bacteria, such as cheese production and fermentative synthesis of chemicals. None the less, the use of bacteriophages may soon replace current antibiotics in the treatment of bacterial infections.