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[[Image:E coli at 10000x, INDIA WESTERMAN RULES! original.jpg|thumb|250px|right|A cluster of ''[[Escherichia coli]]'' [[Bacterium|bacteria]] magnified 10,000 times.]]
[[Image:E coli at 10000x, original.jpg|thumb|250px|right|A cluster of ''[[Escherichia coli]]'' [[Bacterium|bacteria]] magnified 10,000 times.]]
A '''microorganism''' (from the {{lang-el|μικρός}}, ''mikrós'', "small" and ὀργανισμός, ''organismós'', "organism"; also spelled '''micro organism''' or '''micro-organism''') or '''microbe''' is an [[organism]] that is [[microscopic]] (usually too small to be seen by the naked human eye). The study of microorganisms is called [[microbiology]], a subject that began with [[Anton van Leeuwenhoek]]'s discovery of microorganisms in 1675, using a [[microscope]] of his own design.
A '''microorganism''' (from the {{lang-el|μικρός}}, ''mikrós'', "small" and ὀργανισμός, ''organismós'', "organism"; also spelled '''micro organism''' or '''micro-organism''') or '''microbe''' is an [[organism]] that is [[microscopic]] (usually too small to be seen by the naked human eye). The study of microorganisms is called [[microbiology]], a subject that began with [[Anton van Leeuwenhoek]]'s discovery of microorganisms in 1675, using a [[microscope]] of his own design.


Revision as of 17:33, 19 October 2008

A cluster of Escherichia coli bacteria magnified 10,000 times.

A microorganism (from the Greek: μικρός, mikrós, "small" and ὀργανισμός, organismós, "organism"; also spelled micro organism or micro-organism) or microbe is an organism that is microscopic (usually too small to be seen by the naked human eye). The study of microorganisms is called microbiology, a subject that began with Anton van Leeuwenhoek's discovery of microorganisms in 1675, using a microscope of his own design.

Microorganisms are incredibly diverse and include bacteria, fungi, archaea, and protists, as well as some microscopic plants and animals such as plankton, and popularly-known animals such as the planarian and the amoeba. Many scientists would not include viruses and prions, which are often classified as non-living[1][2]. Most microorganisms are single-celled, or unicellular, but some multicellular organisms are microscopic, while some unicellular protists, and some bacteria including Thiomargarita namibiensis are visible to the naked eye.

Microorganisms live in all parts of the biosphere where there is liquid water, including hot springs, on the ocean floor, high in the atmosphere and deep inside rocks within the Earth's crust. Microorganisms are critical to nutrient recycling in ecosystems as they act as decomposers. As some microorganisms can fix nitrogen, they are a vital part of the nitrogen cycle, and recent studies indicate that airborne microbes may play a role in precipitation and weather.[3]

Microbes are also exploited by people in biotechnology, both in traditional food and beverage preparation, and in modern technologies based on genetic engineering. However, pathogenic microbes are harmful, since they invade and grow within other organisms, causing diseases that kill millions of people, other animals, and plants.[4]

History

Evolution

Further information: [[:Timeline of evolution]]

Single-celled microorganisms were the first forms of life to develop on earth, approximately 3–4 billion years ago.[5][6][7] Further evolution was slow,[8] and for about 3 billion years in the Precambrian eon, all organisms were microscopic.[9] So, for most of the history of life on Earth the only form of life were microorganisms.[10] Bacteria, algae and fungi have been identified in amber that is 220 million years old, which shows that the morphology of microorganisms has changed little since the triassic period.[11]

Most microorganisms can reproduce rapidly and microbes such as bacteria can also freely exchange genes by conjugation, transformation and transduction between widely-divergent species.[12] This horizontal gene transfer, coupled with a high mutation rate and many other means of genetic variation, allows microorganisms to swiftly evolve (via natural selection) to survive in new environments and respond to environmental stresses. This rapid evolution is important in medicine, as it has led to the recent development of 'super-bugs' — pathogenic bacteria that are resistant to modern antibiotics.[13]

Pre-Microbiology

The possibility that microorganisms might exist was discussed for many centuries before their actual discovery in the 17th century. The first ideas about microorganisms were those of the Roman scholar Marcus Terentius Varro in a 1st century BC book titled On Agriculture in which he warns against locating a homestead near swamps:

…and because there are bred certain minute creatures which cannot be seen by the eyes, which float in the air and enter the body through the mouth and nose and there cause serious diseases.[14]

This passage seems to indicate that the ancients were aware of the possibility that diseases could be spread by yet unseen organisms.

In The Canon of Medicine (1020), Abū Alī ibn Sīnā (Avicenna) stated that bodily secretion is contaminated by foul foreign earthly bodies before being infected.[15] He also hypothesized that tuberculosis and other diseases might be contagious, i.e. that they were infectious diseases, and used quarantine to limit their spread.[16]

When the Black Death bubonic plague reached al-Andalus in the 14th century, Ibn Khatima wrote that infectious diseases were caused by contagious "minute bodies" that enter the human body.[15] Later, in 1546, Girolamo Fracastoro proposed that epidemic diseases were caused by transferable seedlike entities that could transmit infection by direct or indirect contact, or even without contact over long distances.

All these early claims about the existence of microorganisms were speculative in nature and not based on any data or science. Microorganisms were neither proven, observed, nor correctly and accurately described until the 17th century. The reason for this was that all these early inquiries lacked the most fundamental tool in order for microbiology and bacteriology to exist as a science, and that was the microscope.

Discovery

Antonie van Leeuwenhoek, the first microbiologist and the first to observe microorganisms using a microscope

Anton van Leeuwenhoek was the first person to observe microorganisms, using a microscope of his own design, thereby making him the first microbiologist. In doing so Leeuwenhoek would make one of the most important contributions to biology and open up the fields of microbiology and bacteriology. Prior to Leeuwenhoek's discovery of microorganisms in 1675, it had been a mystery as to why grapes could be turned into wine, milk into cheese, or why food would spoil. Leeuwenhoek did not make the connection between these processes and microorganisms, but using a microscope, he did establish that there were forms of life that were not visible to the naked eye.[17][18] Leeuwenhoek's discovery, along with subsequent observations by Lazzaro Spallanzani and Louis Pasteur, ended the long-held belief that life spontaneously appeared from non-living substances during the process of spoilage.

Lazzarro Spallanzani found that microorganisms could only settle in a broth if the broth was exposed to the air. He also found that boiling the broth would sterilise it and kill the microorganisms. Louis Pasteur expanded upon Spallanzani's findings by exposing boiled broths to the air, in vessels that contained a filter to prevent all particles from passing through to the growth medium, and also in vessels with no filter at all, with air being admitted via a curved tube that would not allow dust particles to come in contact with the broth. By boiling the broth beforehand, Pasteur ensured that no microorganisms survived within the broths at the beginning of his experiment. Nothing grew in the broths in the course of Pasteur's experiment. This meant that the living organisms that grew in such broths came from outside, as spores on dust, rather than spontaneously generated within the broth. Thus, Pasteur dealt the death blow to the theory of spontaneous generation and supported germ theory.

In 1876, Robert Koch established that microbes can cause disease. He did this by finding that the blood of cattle who were infected with anthrax always had large numbers of Bacillus anthracis. Koch also found that he could transmit anthrax from one animal to another by taking a small sample of blood from the infected animal and injecting it into a healthy one, causing the healthy animal to become sick. He also found that he could grow the bacteria in a nutrient broth, inject it into a healthy animal, and cause illness. Based upon these experiments, he devised criteria for establishing a causal link between a microbe and a disease in what are now known as Koch's postulates.[19] Though these postulates cannot be applied in all cases, they do retain historical importance in the development of scientific thought and can still be used today.[20]

Classification and structure

Evolutionary tree showing the common ancestry of all three domains of life.[21] Bacteria are colored blue, eukaryotes red, and archaea green. Relative positions of some phyla are shown around the tree.

Microorganisms can be found almost anywhere in the taxonomic organization of life on the planet. Bacteria and archaea are almost always microscopic, while a number of eukaryotes are also microscopic, including most protists, some fungi, as well as some animals and plants. Viruses are generally regarded as not living and therefore are not microbes, although the field of microbiology also encompasses the study of viruses.

Prokaryotes

Prokaryotes are organisms that lack a cell nucleus and the other organelles found in eukaryotes. Prokaryotes are almost always unicellular, although some species such as myxobacteria can aggregate into complex structures as part of their life cycle. These organisms are divided into two groups, the archaea and the bacteria.

Bacteria

Main article: Bacteria
Staphylococcus aureus bacteria magnified about 10,000x

Bacteria are the most diverse and abundant group of organisms on Earth. Bacteria inhabit practically all environments where some liquid water is available and the temperature is below +140 °C. They are found in sea water, soil, air, animals' gastrointestinal tracts, hot springs and even deep beneath the Earth's crust in rocks.[22] Practically all surfaces which have not been specially sterilized are covered in bacteria. The number of bacteria in the world is estimated to be around five million trillion trillion, or 5 × 1030.[23]

Bacteria are practically all invisible to the naked eye, with a few extremely rare exceptions, such as Thiomargarita namibiensis.[24] They are unicellular organisms and lack membrane-bound organelles. Their genome is usually a single loop of DNA, although they can also harbor small pieces of DNA called plasmids. These plasmids can be transferred between cells through bacterial conjugation. Bacteria are surrounded by a cell wall, which provides strength and rigidity to their cells. They reproduce by binary fission or sometimes by budding, but do not undergo sexual reproduction. Some species form extraordinarily resilient spores, but for bacteria this is a mechanism for survival, not reproduction. Under optimal conditions bacteria can grow extremely rapidly and can double as quickly as every 10 minutes.[25]

Archaea

Main article: Archaea

Archaea are also single-celled organisms that lack nuclei. In the past, the differences between bacteria and archaea were not recognised and archaea were classified with bacteria as part of the kingdom Monera. However, in 1990 the microbiologist Carl Woese proposed the three-domain system that divided living things into bacteria, archaea and eukaryotes.[26] Archaea differ from bacteria in both their genetics and biochemistry. For example, while bacterial cell membranes are made from phosphoglycerides with ester bonds, archaean membranes are made of ether lipids.[27]

Archaea were originally described in extreme environments, such as hot springs, but have since been found in all types of habitats.[28] Only now are scientists beginning to appreciate how common archaea are in the environment, with crenarchaeota being the most common form of life in the ocean, dominating ecosystems below 150 m in depth.[29][30] These organisms are also common in soil and play a vital role in ammonia oxidation.[31]

Eukaryotes

Main article: Eukaryote
File:Chaos diffluens.jpg
An amoeba, a typical eukaryotic microorganism

All living things which are individually visible to the naked eye are eukaryotes (with few exceptions, such as Thiomargarita namibiensis), including humans. However, a large number of eukaryotes are also microorganisms. Unlike bacteria and archaea, eukaryotes contain organelles such as the cell nucleus, the Golgi apparatus and mitochondria in their cells. The nucleus is an organelle which houses the DNA that makes up a cell's genome. DNA itself is arranged in complex chromosomes.[32] Mitochondria are organelles vital in metabolism as they are the site of the citric acid cycle and oxidative phosphorylation. They evolved from symbiotic bacteria and retain a remnant genome.[33] Like bacteria, plant cells have cell walls, and contain organelles such as chloroplasts in addition to the organelles in other eukaryotes. Chloroplasts produce energy from light by photosynthesis, and were also originally symbiotic bacteria.[33]

Unicellular eukaryotes are those eukaryotic organisms that consist of a single cell throughout their life cycle. This qualification is significant since most multicellular eukaryotes consist of a single cell called a zygote at the beginning of their life cycles. Microbial eukaryotes can be either haploid or diploid, and some organisms have multiple cell nuclei (see coenocyte). However, not all microorganisms are unicellular as some microscopic eukaryotes are made from multiple cells.

Protists

Main article: Protista

Of eukaryotic groups, the protists are most commonly unicellular and microscopic. This is a highly diverse group of organisms that are not easy to classify.[34][35] Several algae species are multicellular protists, and slime molds have unique life cycles that involve switching between unicellular, colonial, and multicellular forms.[36] The number of species of protozoa is uncertain, since we may have identified only a small proportion of the diversity in this group of organisms.[37][38]

A microscopic mite Lorryia formosa.

Animals

Main article: Micro-animals

All animals are multicellular, but some are too small to be seen by the naked eye. Microscopic arthropods include dust mites and spider mites. Microscopic crustaceans include copepods and the cladocera, while many nematodes are too small to be seen with the naked eye. Another particularly common group of microscopic animals are the rotifers, which are filter feeders that are usually found in fresh water. Micro-animals reproduce both sexually and asexually and may reach new habitats as eggs that survive harsh environments that would kill the adult animal. However, some simple animals, such as rotifers and nematodes, can dry out completely and remain dormant for long periods of time.[39]

Fungi

Main article: Fungus

The fungi have several unicellular species, such as baker's yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe). Some fungi, such as the pathogenic yeast Candida albicans, can undergo phenotypic switching and grow as single cells in some environments, and filamentous hyphae in others.[40] Fungi reproduce both asexually, by budding or binary fission, as well by producing spores, which are called conidia when produced asexually, or basidiospores when produced sexually.

Plants

Main article: Plant

The green algae are a large group of photosynthetic eukaryotes that include many microscopic organisms. Although some green algae are classified as protists, others such as charophyta are classified with embryophyte plants, which are the most familiar group of land plants. Algae can grow as single cells, or in long chains of cells. The green algae include unicellular and colonial flagellates, usually but not always with two flagella per cell, as well as various colonial, coccoid, and filamentous forms. In the Charales, which are the algae most closely related to higher plants, cells differentiate into several distinct tissues within the organism. There are about 6000 species of green algae.[41]

Habitats and ecology

Microorganisms are found in almost every habitat present in nature. Even in hostile environments such as the poles, deserts, geysers, rocks, and the deep sea, some types of microorganisms have adapted to the extreme conditions and sustained colonies; these organisms are known as extremophiles. Extremophiles have been isolated from rocks as much as 7 kilometres below the earth's surface,[42] and it has been suggested that the amount of living organisms below the earth's surface may be comparable with the amount of life on or above the surface.[22] Extremophiles have been known to survive for a prolonged time in a vacuum, and can be highly resistant to radiation, which may even allow them to survive in space.[43] Many types of microorganisms have intimate symbiotic relationships with other larger organisms; some of which are mutually beneficial (mutualism), while others can be damaging to the host organism (parasitism). If microorganisms can cause disease in a host they are known as pathogens.

Extremophiles

Main article: Extremophile

Extremophiles are microorganisms which have adapted so that they can survive and even thrive in conditions that are normally fatal to most lifeforms. For example, some species have been found in the following extreme environments:

Extremophiles are significant in different ways. They extend terrestrial life into much of the Earth's hydrosphere, crust and atmosphere, their specific evolutionary adaptation mechanisms to their extreme environment can be exploited in bio-technology, and their very existence under such extreme conditions increases the potential for extraterrestrial life.[51]

Soil microbes

The nitrogen cycle in soils depends on the fixation of atmospheric nitrogen. One way this can occur is in the nodules in the roots of legumes that contain symbiotic bacteria of the genera Rhizobium, Mesorhizobium, Sinorhizobium, Bradyrhizobium, and Azorhizobium.[52]

Symbiotic microbes

Symbiotic microbes

Importance

Microorganisms are vital to humans and the environment, as they participate in the Earth's element cycles such as the carbon cycle and nitrogen cycle, as well as fulfilling other vital roles in virtually all ecosystems, such as recycling other organisms' dead remains and waste products through decomposition. Microbes also have an important place in most higher-order multicellular organisms as symbionts. Many blame the failure of Biosphere 2 on an improper balance of microbes.[53]

Use in food

Main article: Fermentation (food)

Microorganisms are used in brewing, winemaking, baking, pickling and other food-making processes.

They are also used to control the fermentation process in the production of cultured dairy products such as yogurt and cheese. The cultures also provide flavour and aroma, and inhibit undesirable organisms.[54]

Use in water treatment

Main article: Sewage treatment

Specially-cultured microbes are used in the biological treatment of sewage and industrial waste effluent, a process known as bioaugmentation.[55]

Use in energy

Main articles: Algae fuel, Cellulosic ethanol, and Ethanol fermentation

Microbes are used in fermentation to produce ethanol,[56] and in biogas reactors to produce methane.[57] Scientists are researching the use of algae to produce liquid fuels,[58] and bacteria to convert various forms of agricultural and urban waste into usable fuels.[59]

Use in science

Microbes are also essential tools in biotechnology, biochemistry, genetics, and molecular biology. The yeasts (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe) are important model organisms in science, since they are simple eukaryotes that can be grown rapidly in large numbers and are easily manipulated.[60] They are particularly valuable in genetics, genomics and proteomics.[61][62] Microbes can be harnessed for uses such as creating steroids and treating skin diseases. Scientists are also considering using microbes for living fuel cells,[63] and as a solution for pollution.[64]

Use in warfare

Main article: Biological warfare

In the Middle Ages, diseased corpses were thrown into castles during sieges using catapults or other siege engines. Individuals near the corpses were exposed to the deadly pathogen and were likely to spread that pathogen to others.[65]

Importance in human health

Human digestion

Further information: Human flora § Human bacterial flora and human health

Microorganisms can form an endosymbiotic relationship with other, larger organisms. For example, the bacteria that live within the human digestive system contribute to gut immunity, synthesise vitamins such as folic acid and biotin, and ferment complex indigestible carbohydrates.[66]

Diseases and immunology

Main article: Pathogenic microbes

Microorganisms are the cause of many infectious diseases. The organisms involved include pathogenic bacteria, causing diseases such as plague, tuberculosis and anthrax; protozoa, causing diseases such as malaria, sleeping sickness and toxoplasmosis; and also fungi causing diseases such as ringworm, candidiasis or histoplasmosis. However, other diseases such as influenza, yellow fever or AIDS are caused by pathogenic viruses, which are not usually classified as living organisms and are not therefore microorganisms by the strict definition. As of 2007, no clear examples of archaean pathogens are known,[67] although a relationship has been proposed between the presence of some methanogens and human periodontal disease.[68]

Importance in ecology

Further information: Decomposition

Microbes are critical to the processes of decomposition required to cycle nitrogen and other elements back to the natural world.

Hygiene

Main article: Hygiene

Hygiene is the avoidance of infection or food spoiling by eliminating microorganisms from the surroundings. As microorganisms, particularly bacteria, are found practically everywhere, this means in most cases the reduction of harmful microorganisms to acceptable levels. However, in some cases it is required that an object or substance be completely sterile, i.e. devoid of all living entities and viruses. A good example of this is a hypodermic needle.

In food preparation microorganisms are reduced by preservation methods (such as the addition of vinegar), clean utensils used in preparation, short storage periods or by cool temperatures. If complete sterility is needed, the two most common methods are irradiation and the use of an autoclave, which resembles a pressure cooker.

There are several methods for investigating the level of hygiene in a sample of food, drinking water, equipment etc. Water samples can be filtrated through an extremely fine filter. This filter is then placed in a nutrient medium. Microorganisms on the filter then grow to form a visible colony. Harmful microorganisms can be detected in food by placing a sample in a nutrient broth designed to enrich the organisms in question. Various methods, such as selective media or PCR, can then be used for detection. The hygiene of hard surfaces, such as cooking pots, can be tested by touching them with a solid piece of nutrient medium and then allowing the microorganisms to grow on it.

There are no conditions where all microorganisms would grow, and therefore often several different methods are needed. For example, a food sample might be analyzed on three different nutrient mediums designed to indicate the presence of "total" bacteria (conditions where many, but not all, bacteria grow), molds (conditions where the growth of bacteria is prevented by e.g. antibiotics) and coliform bacteria (these indicate a sewage contamination).

In fiction

Microorganisms have frequently played an important part in science fiction, both as agents of disease, and as entities in their own right.

Some notable uses of microorganisms in fiction include:

  • The War of the Worlds, where microorganisms play important thematic and plot-related roles.
  • Fantastic Voyage, in which some scientists are miniaturised to microscopic size and observe micro-organisms from a new perspective
  • Blood Music, in which a colony of microorganisms is given intelligence
  • The Andromeda Strain, in which extraterrestrial microorganisms kill several people
  • The White Plague, is created and released in vengeance by John Roe O'Neill for the death of his wife and children, it is designed to kill only women.
  • Twelve Monkeys, James Cole (Bruce Willis) searches for a pure germ in the past, which creates a deadly plague in the future. Also, Brad Pitt (as Jeffery Goines) discusses his germaphobia.

See also

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  38. ^ Moreira D, López-García P (2002). "The molecular ecology of microbial eukaryotes unveils a hidden world". Trends Microbiol. 10 (1): 31–8. doi:10.1016/S0966-842X(01)02257-0. PMID 11755083.
  39. ^ Lapinski J, Tunnacliffe A (2003). "Anhydrobiosis without trehalose in bdelloid rotifers". FEBS Lett. 553 (3): 387–90. doi:10.1016/S0014-5793(03)01062-7. PMID 14572656.
  40. ^ Kumamoto CA, Vinces MD (2005). "Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence". Cell. Microbiol. 7 (11): 1546–54. doi:10.1111/j.1462-5822.2005.00616.x. PMID 16207242.
  41. ^ Thomas, D. 2002. Seaweeds. The Natural History Museum, London. ISBN 0 565 09175 1
  42. ^ Szewzyk U, Szewzyk R, Stenström T (1994). "Thermophilic, anaerobic bacteria isolated from a deep borehole in granite in Sweden". Proc Natl Acad Sci U S A. 91 (5): 1810–3. doi:10.1073/pnas.91.5.1810. PMID 11607462.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  43. ^ Horneck G (1981). "Survival of microorganisms in space: a review". Adv Space Res. 1 (14): 39–48. doi:10.1016/0273-1177(81)90241-6. PMID 11541716.
  44. ^ Strain 121, a hyperthermophilic archaea, has been shown to reproduce at 121 °C (250 °F), and survive at 130 °C (266 °F).[2]
  45. ^ Some Psychrophilic bacteria can grow at −17 °C (1 °F),[3] and can survive near absolute zero.[4]
  46. ^ Picrophilus can grow at pH -0.06.[5]
  47. ^ The alkaliphilic bacteria Bacillus alcalophilus can grow at up to pH 11.5.[6]
  48. ^ Dyall-Smith, Mike, HALOARCHAEA, University of Melbourne. See also Haloarchaea.
  49. ^ The piezophilic bacteria Halomonas salaria requires a pressure of 1,000 atm; nanobes, a speculative organism, have been reportedly found in the earth's crust at 2,000 atm.[7]
  50. ^ See Deinococcus radiodurans
  51. ^ Cavicchioli R., Extremophiles and the search for extraterrestrial life. Astrobiology. 2002 Fall;2(3):281-92.
  52. ^ Barea J, Pozo M, Azcón R, Azcón-Aguilar C (2005). "Microbial co-operation in the rhizosphere". J Exp Bot. 56 (417): 1761–78. doi:10.1093/jxb/eri197. PMID 15911555.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  53. ^ Gillen, Alan L. (2007). The Genesis of Germs: The Origin of Diseases and the Coming Plagues. New Leaf Publishing Group. p. 10. ISBN 0-890-51493-3.
  54. ^ "Dairy Microbiology". University of Guelph. Retrieved 2006-10-09.
  55. ^ Gray, N.F. (2004). Biology of Wastewater Treatement. Imperial College Press. p. 1164. ISBN 1-860-94332-2.
  56. ^ Kitani, Osumu and Carl W. Hall (1989). Biomass Handbook. Taylor & Francis US. p. 256. ISBN 2-881-24269-3.
  57. ^ Pimental, David (2007). Food, Energy, and Society. CRC Press. p. 289. ISBN 1-420-04667-5.
  58. ^ Tickell, Joshua; et al. (2000). From the Fryer to the Fuel Tank: The Complete Guide to Using Vegetable Oil as an Alternative Fuel. Biodiesel America. p. 53. ISBN 0-970-72270-2. {{cite book}}: Explicit use of et al. in: |author= (help)
  59. ^ Inslee, Jay; et al. (2008). Apollo's Fire: Igniting America's Clean Energy Economy. Island Press. p. 157. ISBN 1-597-26175-0. {{cite book}}: Explicit use of et al. in: |author= (help)
  60. ^ Castrillo JI, Oliver SG (2004). "Yeast as a touchstone in post-genomic research: strategies for integrative analysis in functional genomics". J. Biochem. Mol. Biol. 37 (1): 93–106. PMID 14761307.
  61. ^ Suter B, Auerbach D, Stagljar I (2006). "Yeast-based functional genomics and proteomics technologies: the first 15 years and beyond". BioTechniques. 40 (5): 625–44. PMID 16708762.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  62. ^ Sunnerhagen P (2002). "Prospects for functional genomics in Schizosaccharomyces pombe". Curr. Genet. 42 (2): 73–84. doi:10.1007/s00294-002-0335-6. PMID 12478386.
  63. ^ Soni, S.K. (2007). Microbes: A Source of Energy for 21st Century. New India Publishing. ISBN 8-189-42214-6.
  64. ^ Moses, Vivian; et al. (1999). Biotechnology: The Science and the Business. CRC Press. p. 563. ISBN 9-057-02407-1. {{cite book}}: Explicit use of et al. in: |author= (help)
  65. ^ Langford, Roland E. (2004). Introduction to Weapons of Mass Destruction: Radiological, Chemical, and Biological. Wiley-IEEE. p. 140. ISBN 0-471-46560-7.
  66. ^ O'Hara A, Shanahan F (2006). "The gut flora as a forgotten organ". EMBO Rep. 7 (7): 688–93. doi:10.1038/sj.embor.7400731. PMID 16819463.
  67. ^ Eckburg P, Lepp P, Relman D (2003). "Archaea and their potential role in human disease". Infect Immun. 71 (2): 591–6. doi:10.1128/IAI.71.2.591-596.2003. PMID 12540534.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  68. ^ Lepp P, Brinig M, Ouverney C, Palm K, Armitage G, Relman D (2004). "Methanogenic Archaea and human periodontal disease". Proc Natl Acad Sci U S A. 101 (16): 6176–81. doi:10.1073/pnas.0308766101. PMID 15067114.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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