The term micro-organism encompasses a broad range of microscopic organisms, most notably bacteria, viruses and fungi as well as protazoans. Although many people perceive micro-organisms as negative entities, they are in fact normal inhabitants of humans. We were initially born as sterile individuals with the first microbial exposure through the passage through the birth canal. After this, the human microflora becomes increasingly more complex as time progresses until the age of two when the microbiota becomes more stable with a larger proportion on anaerobic microbes (Dicksved and Jansson, 2010).
Figure 1: Scanning electron microscope image of B. thetaiotaomicron, a prominent bacterium in the human gut (Gross, L., 2007)
It is only under circumstances when the body is compromised that some strains of bacteria cause disease since those living on or within the body usually live as commensals, having beneficial effects for the host as well as the bacteria themselves. For example, in the GI tract alone, there are roughly 800-1000 different species of bacteria with more than 7000 different strains (Figure 1). By colonising the gut, these so-called "friendly" bacteria have a wide range of beneficial effects since they are helping to develop the immune system as well as making it progressively more difficult for pathogenic bacteria to colonise due to competition for nutrients and sites of attachment as well as the prevention of digestive conditions such as lactose intolerance, an idea that will be discussed later.http://bytesizebio.net/wp-content/uploads/2009/01/human-gut-em.png
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One of the main reasons that micro-organisms are perceived as detrimental to health is their association with disease with the vast majority of childhood deaths in the recent past due to microbial infection that could have been prevented. Although this is true, the vast majority of micro-organisms living on or within humans are not harmful, with only 0.01% being pathogenic. Conversely, many bacteria are extremely beneficial for health through the production of antibiotics as secondary metabolites that serve as means of preventing microbial infection in humans.HHH
First discovered by Alexander Fleming in 1928, many hundreds of antibiotics have since been isolated which are used everyday for many bacterial infections that previously may have been fatal. In this sense they have revolutionised medical care since death due to previously untreatable microbial disease can now be prevented. For this to occur, antibiotics must have selective toxicity in order to be able to work. This means that the drug must be effective against the pathogenic agent but have minimal or no toxicity to humans (Kenneth Todar, 2009).
An example of this is the exploitation of the differences between the ribosomes of prokaryotic and eukaryotic organisms in both size and RNA sequences. This means a variety of antibiotics can be used that inhibit the growth or induce death in bacteria without inhibiting ribosomes in eukaryotic cells thus playing a critical medicinal role in modern healthcare. An example of this is chloramphenicol which was derived from the bacterium Streptomyces venezuela. This antibiotic works by binding to 23S rRNA present in 70S ribosomes and inhibiting its role in the formation of peptide bonds through the enzyme peptidyl transferase (Granner and Weil, 2006). This brings about the death of bacteria since protein synthesis has been stopped.
However, not all antibiotics are recognised to be universally safe. Chloramphenciol was once commonly used for a wide variety of bacterial infections as it is a broad-spectrum antibiotic meaning that it acts against both Gram-positive and Gram-negative bacteria. However, due to severe side effects, this is now an antibiotic of last resort for life-threatening illnesses such as typhoid fever. Concerns for this antibiotic arose due to the development of aplastic anaemia, whereÂ bone marrowÂ does not produce sufficient newÂ cellsÂ to replenishÂ blood cells (British Medical Journal, 1952). Bone marrow cells divide rapidly and as a result, synthesis mitochondria rapidly. This is the major concern since mitochondria contain 70S ribosomes and as such can be affected by the use of any antibiotic which targets prokaryotic ribosomes such as chloramphenciol.
However, should there be a breach of the body's natural defences by micro-organisms, the specific host defences are stimulated. This involves the production of antibodies from plasma cells around 15 days after infection which recognise antigens on the cell surface membrane of pathogens, bind to them causing their agglutination so that they are more easily recognised by phagocytes and destroyed. These antibodies remain in the body as memory cells after the initial primary infection thus are an important means of protection against the disease should a person come into contact with the same pathogen in the future. It is this form of acquired immunity that is the basis of vaccination today.
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Figure 2: Annual measles notifications and vaccine coverage, England and Wales 1950-2007 (Health Protection Agency)Vaccination has been a key solution to reduce the incidence and mortality of infectious diseases not only protecting the individual against diseases but also the wider community. For example, measles is the result of a highly virulent paramyxovirus, Morbillivirus. Cases of measles dropped after t he introduction of the MMR vaccine in 1988 although in recent years, although there have been increasing number of cases: for example,Â in 2009 there wereÂ 1143 casesÂ of measlesÂ in England and Wales compared with 70 casesÂ in 2001 (NHS Online, 2010). This is because protection on a wider scale requires 95% of the population to be vaccinated against the disease in order to reduce the risk of an epidemic within a population which is clearly shown in Figure 2 (around 85% uptake rate) hence a rise in incidence rate.
There are a variety of vaccines available such as attenuated vaccines or vaccines that contain antigens or toxoids, all of which have a different method of introducing the pathogen into the body. For example, attenuated vaccines such as the vaccine given to prevent Poliomyelitis, introduces a weakened form of the pathogen into the bloodstream so that the pathogen cannot cause disease but is still active enough to stimulate the immune system into making antibodies. Occasionally, it is the toxin released by the organism, not the organism itself that causes disease; this is the case in Tetanus caused by the bacteriumÂ Clostridium tetani. In this case, toxoid vaccines are used where the toxin is treated chemically so that the protein product is denatured and so cannot cause disease but still retains some epitopes (part of the surface of the antigen that binds to the antibody) on the molecule that will be recognised by B cells which will subsequently stimulated into making antibodies (Kimball, 1994).
There are many other beneficial uses of micro-organisms, for example, the use of bacteria in food production. This is primarily done in dairy product production such as cheese or yoghurt although yeasts are also used in the production of bread and the fermentation of beer. For example, Lactobacillus acidophilus is one of the most common species of bacteria that are used in the production of live yoghurt although other Lactobacillus species are also used such as Lactobacillus bulgaricus as a yoghurt starter.
In recent years, there has been a dramatic rise in studies conducted to evaluate the benefits of probiotics in food that would then have beneficial effects on the consumer ranging from improved lactose breakdown, alleviating infectious diseases among those at risk to lowering cholesterol. The World Health Organisation defines probiotics as "live micro-organisms which when administered in adequate amounts confer a health benefit on the host." (Joint FAO/WHO Expert Consultation, 2001)
For example, an increasing number of dairy products such as Yakult and Actimel yoghurt drinks have been cultured with Lactobacillus species as probiotics such as Lactobacillus casei. It is these strains of probiotic that has been identified as a reliever of the symptoms of lactose intolerance through the production of the enzyme Î²-galactosidase which is able to hydrolyse the gycosidic bonds in lactose thus reducing the effects of lactose intolerance during digestion (Gilliland, 2001).
On the other hand, bacteria are predominantly used in recombinant DNA technology. This is the process by which large quantities of a desired protein are produced through the introduction of the gene coding for the protein into a vector which can be cloned. These genes can be inserted into a variety of vectors; however the most common are plasmids. http://www.bio.davidson.edu/courses/Molbio/MolStudents/spring99/alex/PLASMID.gif
Figure 3: Process of cloning into a plasmid. The desired gene and vector are cut using a restriction enzyme, ligated together and transformed into bacteria before the clones are identified and purified. (Caudwell, A.)Plasmids are small circular rings of extra-chromosomal DNA that replicate autonomously of the chromosomal DNA and are present within bacteria, yeasts and archaea. Since they are small, they can be easily manipulated for beneficial use in biotechnology as vectors where their ability to be spliced open and have foreign DNA inserted into is taken full advantage of (Figure 3). This is because the plasmid replicates independently within the bacterium host thus allowing the reproduction of foreign DNA protein quickly and easily using the bacterial replication process before clones can be selected and purified.
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This process has been used to aid the production of many protein products such as human growth hormone (used to treat dwarfism), human insulin (used to treat diabetes) and clotting factor VIII (used to restore haemostasis).The development of this technology has allowed for possible harmful effects of alternative sources of the proteins to eradicated as well as the quick and easy production of the protein. For example, human insulin previously was obtained from the pancreas of cattle and pig which often caused the sufferer to become sensitised to the insulin they were using whereas human growth hormone was collected from cadavers which was a lengthy and time-consuming process.
However, none of this would be possible were it not for nitrogen-fixing bacteria since the growth of all organisms whether eukaryotic or prokaryotic, is dependent on nitrogen; it is this single element that is often the limiting factor of growth within an environment. The biological importance of nitrogen stems from the fact that is a necessary component of proteins and in the nitrogenous bases that DNA and RNA are made from as well as other cellular components.
Fig 4: Biological nitrogen fixation suing the nitrogenase enzyme complex (Deacon, J.)Although the vast majority of the atmospheric gas is composed of nitrogen (around 70%), this is unavailable as it is in its elemental form. The strong triple bond between the two atoms makes nitrogen an inert gas and so cannot be used. Because of this, atmospheric nitrogen has to be first converted into other organic forms such as nitrite, nitrate or ammonium which can then be used; however, these compounds are usually in short supply and high demand thus the reason why nitrogen is the limiting factor of growth. Biological nitrogen fixation is solely due to prokaryotes- namely Azotobacter and Rhizobium species which use the nitrogenase enzyme complex which produces 2 moles of ammonia from one mole of nitrogen gas, utilising 16 moles of ATP (Figure 4). This can occur in two forms: symbiotically and non-symbiotically.
Rhizobia are bacteria that live symbiotically in the root nodules of legumes and fix atmospheric nitrogen into the more usable form of ammonium ions. This act of symbiosis is mutually beneficial for the two parties since there is a constant source of ammonium ions for use whereas the plant provides sufficient oxygen for the reduction of nitrogen, a process aided by the protein leghaemoglobin which reduces the amount of free oxygen which would interfere with the reduction process since the enzyme nitrogenase is irreversibly inactivated by oxygen.
On the other hand, Azotobacter species fix nitrogen non-symbiotically since they are free-living within the soil. These bacteria fix nitrogen in the same way as Rhizobia converting atmospheric nitrogen into alternative organic forms that can be used.
Without this conversion from atmospheric nitrogen to more usable forms, basic biological processes such as DNA replication or growth would not take place since nitrogen is required for this to happen thus is follow that the availability of reduced forms of nitrogen is incredibly important and would not be possible on such a large scale were it not for bacteria.
Although there are negative connotations surrounding micro-organisms due to their association with disease, they also have many varied and beneficial uses for humans, some of which are critical to ensure human survival. It is these uses that have improved medical care immensely through the use of antibiotics and recombinant DNA technology in addition to their uses in everyday circumstances such as food and drink production.