Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic or beta-hemolytic, facultative anaerobic member of the genus Streptococcus. They are found in pairs and do not form spores and are nonmotile; as a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, is the subject of many humoral immunity studies. S. pneumoniae resides asymptomatically in healthy carriers colonizing the respiratory tract and nasal cavity. However, in susceptible individuals with weaker immune systems, such as the elderly and young children, the bacterium may become pathogenic and spread to other locations to cause disease, it spreads by direct person-to-person contact via respiratory droplets and by autoinoculation in persons carrying the bacteria in their upper respiratory tracts. It can be a cause of neonatal infections. S. Pneumoniae is the main cause of community acquired pneumonia and meningitis in children and the elderly, of septicemia in those infected with HIV.
The organism causes many types of pneumococcal infections other than pneumonia. These invasive pneumococcal diseases include bronchitis, acute sinusitis, otitis media, meningitis, osteomyelitis, septic arthritis, peritonitis, pericarditis and brain abscess. S. Pneumoniae can be differentiated from the viridans streptococci, some of which are alpha-hemolytic, using an optochin test, as S. pneumoniae is optochin-sensitive. S. pneumoniae can be distinguished based on its sensitivity to lysis by bile, the so-called "bile solubility test". The encapsulated, Gram-positive, coccoid bacteria have a distinctive morphology on Gram stain, lancet-shaped diplococci, they have a polysaccharide capsule. In 1881, the organism, known in 1886 as the pneumococcus for its role as a cause of pneumonia, was first isolated and independently by the U. S. Army physician the French chemist Louis Pasteur; the organism was termed Diplococcus pneumoniae from 1920 because of its characteristic appearance in Gram-stained sputum.
It was renamed Streptococcus pneumoniae in 1974 because it was similar to streptococci. S. Pneumoniae played a central role in demonstrating that genetic material consists of DNA. In 1928, Frederick Griffith demonstrated transformation of life turning harmless pneumococcus into a lethal form by co-inoculating the live pneumococci into a mouse along with heat-killed virulent pneumococci. In 1944, Oswald Avery, Colin MacLeod, Maclyn McCarty demonstrated that the transforming factor in Griffith's experiment was not protein, as was believed at the time, but DNA. Avery's work marked the birth of the molecular era of genetics; the genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs depending on the strain. It has a core set of 1553 genes, plus 154 genes in its virulome, which contribute to virulence and 176 genes that maintain a noninvasive phenotype. Genetic information can vary up to 10% between strains. Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium.
Transformation is a complex developmental process requiring energy and is dependent on expression of numerous genes. In S. pneumoniae, at least 23 genes are required for transformation. For a bacterium to bind, take up, recombine exogenous DNA into its chromosome, it must enter a special physiological state called competence. Competence in S. pneumoniae is induced by DNA-damaging agents such as mitomycin C, fluoroquinolone antibiotics, topoisomerase inhibitors. Transformation protects S. pneumoniae against the bactericidal effect of mitomycin C. Michod et al. summarized evidence that induction of competence in S. pneumoniae is associated with increased resistance to oxidative stress and increased expression of the RecA protein, a key component of the recombinational repair machinery for removing DNA damages. On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damages. S. pneumoniae infection stimulates polymorphonuclear leukocytes to produce an oxidative burst, lethal to the bacteria.
The ability of S. pneumoniae to repair the oxidative DNA damages in its genome, caused by this host defense contributes to this pathogen’s virulence. Consistent with this premise, Li et al. reported that, among different transformable S. pneumoniae isolates, nasal colonization fitness and virulence depend on an intact competence system. S. pneumoniae is part of the normal upper respiratory tract flora. As with many natural flora, it can become pathogenic under the right conditions when the immune system of the host is suppressed. Invasins, such as pneumolysin, an antiphagocytic capsule, various adhesins, immunogenic cell wall components are all major virulence factors. After S. pneumoniae colonizes the air sacs of the lungs, the body responds by stimulating the inflammatory response, causing plasma and white blood cells to fill the alveoli. This condition is called pneumonia, it is susceptible to clindamycin. Pneumonia is the most common of the S. pneumoniae diseases which include symptoms such as fever and chills, rapid breathing, difficulty breathing, chest pain.
For the elderly, they may include confusion, low alertness, the former listed symptoms to a lesser degree. Pneumococcal me
T-even phages known as the E. coli phages, are a group of double-stranded DNA bacteriophages from the family Myoviridae. Bacteriophage means to "eat bacteria", phages are well known for being obligate intracellular parasites that reproduce within the host cell and are released when the host is destroyed by lysis. Containing about 160 genes, these virulent viruses are among the largest, most complex viruses that are known and one of the best studied model organisms, they have played a key role in the development of molecular biology. Bacteriophages were first discovered by the English scientist Frederick Twort in 1915 and Félix d'Hérelle in 1917. In the late 1930s, T. L. Rakieten proposed either a mixture of raw sewerage or a lysate from E.coli infected with raw sewerage to the two researchers Milislav Demerac and Ugo Fano. These two researchers isolated T3, T4, T5, T6 from E.coli. In 1932, the researcher J. Bronfenbrenner had studied and worked on the T2 phage, at which the T2 phage was isolated from the virus.
This isolation was made from a fecal material rather than from sewerage. At any rate, Delbruck was involved in the discovery of the T phages, his part was naming the bacteriophages into Type 2, Type 3, etc.. Phages have multiple factors contributing to their structure, it consists of the head, helical sheath, the core or tube, hexagonal base plate, tail fibers and tail pins. The head's job surround nucleic acids; the tail fibers help in attaching the phage to a bacterial cell. The tail acts as a duct; the collar helps support the head. Bacteriophages in general contain a head structure, which can vary in shape; the head acts as the protective covering. Certain phages have tails attached to the phage head; the tail is a hollow duct. T-even Bacteriophages have genomes that code for phage-specific DNA replication, DNA repair functions, they offer well branded genes and proteins. Similar to all viruses, they depend on many of their hosts important makeups and roles or functions, for their reproduction. Dating back to the 1940s till date, T-even phages are considered the best studied model organisms.
Model organisms are required to be simple with as few as five genes. Yet, T-even phages are in fact among the largest and highest complexity virus, in which these phages genetic information is made up of around 160 genes. Coincident with their complexity, T-even viruses were found to have an unimaginable feature of no other, the presence of the unusual base hydroxymethylcytosine in place of the nucleic acid base cytosine. In addition to this, the HMC residues on the T-even phage are glucosylated in a specific pattern; this unique feature allowed the formation of new enzymes that never existed in T-even infected cells or any other cell and modifying T-even phage DNA provided a basic underlying advancement in viral and molecular levels. Other unique features of the T-even virus is its regulated gene expression; these unique features and other features gave significance of the T-even phages, this includes transduction, responsible for transfer of drug resistant features, lysogenic conversion is responsible for acquisition of new characteristics such as the formation of new enzymes, random insertion into bacterial chromosome can induce insertional mutation, epidemiological typing of bacteria, phages are used extensively in genetic engineering where they serve as cloning vectors.
Libraries of genes and monoclonal antibodies are maintained in phages. In addition to all this they are responsible for natural removal of bacteria from water bodies. Just like all other viruses, T-even phages don't just randomly attach to the surface of their host; these receptors vary with the phage. In order for the T-even phage to infect its host and begin its life cycle it must enter the first process of infection, adsorption of the phage to the bacterial cell. Adsorption is a value characteristic of phage-host pair and the adsorption of the phage on host cell surface is illustrated as a 2-stage process: reversible and irreversible, it involves the phages tail structure that begins when the phages tail fibers helps bind the phage to the appropriate receptor of its host. This process is reversible. One or more of the components of the base plate mediates irreversible process of binding of the phage to a bacterium. Penetration is a value characteristic of phage-host infection that involves the injection of the phages genetic material inside the bacterium.
Penetration of nucleic acid takes place after the irreversible adsorption phase. Mechanisms involving penetration of the phages nucleic acid are specific for each phage; this penetration mechanism can involve electrochemical membrane potential, ATP molecules, enzymatic splitting of peptidoglycan layer, or all three of these factor can be vital for the penetration of the nucleic acid inside the bacterial cell. Studies have been done on the T2 bacteriophage mechanism of penetration and it has shown that the phages tail does not penetrate inside the bacterial cell wall and penetration of this phage involves electrochemical membrane potential on the inner membrane. Virulent bacteriophages multiply in their bacterial host after entry. After the number of progeny phages re
A super-spreader is a host—an organism infected with a disease—that infects, disproportionately, more secondary contacts than other hosts who are infected with the same disease. A sick human can be a super-spreader. Super-spreaders are thus of high concern in epidemiology; some cases of super-spreading conform to the 20/80 rule, where 20% of infected individuals are responsible for 80% of transmissions, although super-spreading can still be said to occur when super-spreaders account for a higher or lower percentage of transmissions. In epidemics with super-spreading, the majority of individuals infect few secondary contacts. Super-spreading events are shaped by multiple factors including a decline in herd immunity, nosocomial infections, viral load, airflow dynamics, immune suppression, co-infection with another pathogen. Although loose definitions of super-spreading exist, some effort has been made at defining what qualifies as a super-spreading event more explicit. Lloyd-Smith et al. define a protocol to identify a super-spreading event as follows: estimate the effective reproductive number, R, for the disease and population in question.
This protocol defines a 99th-percentile SSE as a case which causes more infections than would occur in 99% of infectious histories in a homogeneous population. During the 2003 SARS outbreak in Beijing, epidemiologists defined a super-spreader as an individual with transmission of SARS to at least eight contacts. Super-spreaders may not show any symptoms of the disease. Super-spreaders have been identified who excrete a higher than normal number of pathogens during the time they are infectious; this causes their contacts to be exposed to higher viral/bacterial loads than would be seen in the contacts of non-superspreaders with the same duration of exposure. The basic reproduction number R0 is the average number of secondary infections caused by a typical infective person in a susceptible population; the basic reproductive number is found by multiplying the average number of contacts by the average probability that a susceptible individual will become infected, called the shedding potential. R0 = Number of contacts X Shedding potential The individual reproductive number represents the number of secondary infections caused by a specific individual during the time that individual is infectious.
Some individuals have higher than average individual reproductive numbers and are known as super-spreaders. Through contact tracing, epidemiologists have identified super-spreaders in measles, rubella, smallpox, Ebola hemorrhagic fever and SARS. Men with HIV who were co-infected with at least one other sexually transmitted disease, such as gonorrhea, hepatitis C, herpes simplex 2 virus, were found to have an eight-fold higher HIV shedding rate than men without co-infection; this shedding rate was calculated in men with similar HIV viral loads. Once treatment for the co-infection had been completed, the HIV shedding rate returned to levels comparable to men without co-infection. Herd immunity, or herd effect, refers to the indirect protection that immunized community members provide to non-immunized members in preventing the spread of contagious disease; the greater the number of immunized individuals, the less an outbreak can occur because there are fewer susceptible contacts. In epidemiology, herd immunity is known as a dependent happening because it influences transmission over time.
As a pathogen that confers immunity to the survivors moves through a susceptible population, the number of susceptible contacts declines. If susceptible individuals remain, their contacts are to be immunized, preventing any further spread of the infection; the proportion of immune individuals in a population above which a disease may no longer persist is the herd immunity threshold. Its value varies with the virulence of the disease, the efficacy of the vaccine, the contact parameter for the population; that is not to say that an outbreak can't occur. The first cases of SARS occurred in mid-November 2002 in the Guangdong Province of China; this was followed by an outbreak in Hong Kong in February, 2003. A Guangdong Province doctor, Liu Jianlun, who had treated SARS cases there, had contracted the virus and was symptomatic. Despite his symptoms, he traveled to Hong Kong to attend a family wedding, he stayed on the ninth floor of the Metropole Hotel in Kowloon, infecting 16 other hotel guests staying on that floor.
The guests traveled to Canada, Singapore and Vietnam, spreading SARS to those locations and transmitting what became a global epidemic. In another case during this same outbreak, a 54-year-old male was admitted to a hospital with coronary heart disease, chronic renal failure and type two diabetes, he had been in contact with a patient known to have SARS. Shortly after his admission he developed fever, cough and sore throat; the admitting physician suspected SARS. The patient was transferred to another hospital for treatment of his coronary artery disease. While there, his SARS symptoms became more pronounced, it was discovered he had transmitted SARS to 33 other patients in just two days. He was transferred back to the original hospital where he died of SARS; the SARS pandemic was contained, but not before it caused 8,273 cases and 775 deat
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of plasma membrane, which buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes phagocytosis, it is a form of active transport. The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis, caveolae and phagocytosis. Clathrin-mediated endocytosis is mediated by the production of small vesicles that have a morphologically characteristic coat made up of the cytosolic protein clathrin. Clathrin-coated vesicles are found in all cells and form domains of the plasma membrane termed clathrin-coated pits. Coated pits can concentrate large extracellular molecules that have different receptors responsible for the receptor-mediated endocytosis of ligands, e.g. low density lipoprotein, growth factors and many others.
Study in mammalian cells confirm a reduction in clathrin coat size in an increased tension environment. In addition, it suggests that the two distinct clathrin assembly modes, namely coated pits and coated plaques, observed in experimental investigations might be a consequence of varied tensions in the plasma membrane. Caveolae are the most common reported non-clathrin-coated plasma membrane buds, which exist on the surface of many, but not all cell types, they consist of the cholesterol-binding protein caveolin with a bilayer enriched in cholesterol and glycolipids. Caveolae are small flask-shape pits in the membrane, they can constitute up to a third of the plasma membrane area of the cells of some tissues, being abundant in smooth muscle, type I pneumocytes, fibroblasts and endothelial cells. Uptake of extracellular molecules is believed to be mediated via receptors in caveolae. Potocytosis is a form of receptor-mediated endocytosis that uses caveolae vesicles to bring molecules of various sizes into the cell.
Unlike most endocytosis that uses caveolae to deliver contents of vesicles to lysosomes or other organelles, material endocytosed via potocytosis is released into the cytosol. Pinocytosis, which occurs from ruffled regions of the plasma membrane, is the invagination of the cell membrane to form a pocket, which pinches off into the cell to form a vesicle filled with a large volume of extracellular fluid and molecules within it; the filling of the pocket occurs in a non-specific manner. The vesicle travels into the cytosol and fuses with other vesicles such as endosomes and lysosomes. Phagocytosis is the process by which cells bind and internalize particulate matter larger than around 0.75 µm in diameter, such as small-sized dust particles, cell debris, micro-organisms and apoptotic cells. These processes involve the uptake of larger membrane areas than clathrin-mediated endocytosis and caveolae pathway. More recent experiments have suggested that these morphological descriptions of endocytic events may be inadequate, a more appropriate method of classification may be based upon the clathrin-dependence of particular pathways, with multiple subtypes of clathrin-dependent and clathrin-independent endocytosis.
Mechanistic insight into non-phagocytic, clathrin-independent endocytosis has been lacking, but a recent study has shown how Graf1 regulates a prevalent clathrin-independent endocytic pathway known as the CLIC/GEEC pathway. The endocytic pathway of mammalian cells consists of distinct membrane compartments, which internalize molecules from the plasma membrane and recycle them back to the surface, or sort them to degradation; the principal components of the endocytic pathway are: Early endosomes are the first compartment of the endocytic pathway. Early endosomes are located in the periphery of the cell, receive most types of vesicles coming from the cell surface, they have a characteristic tubulo-vesicular structure and a mildly acidic pH. They are principally sorting organelles where many endocytosed ligands dissociate from their receptors in the acid pH of the compartment, from which many of the receptors recycle to the cell surface, it is the site of sorting into transcytotic pathway to compartments via transvesicular compartments.
Late endosomes receive endocytosed material en route to lysosomes from early endosomes in the endocytic pathway, from trans-Golgi network in the biosynthetic pathway, from phagosomes in the phagocytic pathway. Late endosomes contain proteins characteristic of nucleosomes, mitochondria and mRNAs including lysosomal membrane glycoproteins and acid hydrolases, they are acidic, are part of the trafficking pathway of mannose-6-phosphate receptors. Late endosomes are thought to mediate a final set of sorting events prior the delivery of material to lysosomes. Lysosomes are the last compartment of the endocytic pathway, their chief function is to break down cellular waste products, carbohydrates and other macromolecules into simple compounds. These are returned to the cytoplasm as new cell-building materials. To accomplish this, lysosomes use some 40 differe
A model organism is a non-human species, extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are used to research human disease when human experimentation would be unfeasible or unethical; this strategy is made possible by the common descent of all living organisms, the conservation of metabolic and developmental pathways and genetic material over the course of evolution. Studying model organisms can be informative, but care must be taken when generalizing from one organism to another. In researching human disease, model organisms allow for better understanding the disease process without the added risk of harming an actual human; the species chosen will meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed. Although biological activity in a model organism does not ensure an effect in humans, many drugs and cures for human diseases are developed in part with the guidance of animal models.
There are three main types of disease models: homologous and predictive. Homologous animals have the same causes and treatment options as would humans who have the same disease. Isomorphic animals share the same treatments. Predictive models are similar to a particular human disease in only a couple of aspects, but are useful in isolating and making predictions about mechanisms of a set of disease features; the use of animals in research dates back to ancient Greece, with Aristotle and Erasistratus among the first to perform experiments on living animals. Discoveries in the 18th and 19th centuries included Antoine Lavoisier's use of a guinea pig in a calorimeter to prove that respiration was a form of combustion, Louis Pasteur's demonstration of the germ theory of disease in the 1880s using anthrax in sheep. Research using animal models has been central to many of the achievements of modern medicine, it has contributed most of the basic knowledge in fields such as human physiology and biochemistry, has played significant roles in fields such as neuroscience and infectious disease.
For example, the results have included the near-eradication of polio and the development of organ transplantation, have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan's work with the fruit fly Drosophila melanogaster identified chromosomes as the vector of inheritance for genes. Drosophila became one of the first, for some time the most used, model organisms, Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science." D. melanogaster remains one of the most used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of William Ernest Castle in collaboration with Abbie Lathrop led to generation of the DBA inbred mouse strain and the systematic generation of other inbred strains; the mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries. In the late 19th century, Emil von Behring isolated the diphtheria toxin and demonstrated its effects in guinea pigs.
He went on to develop an antitoxin against diphtheria in animals and in humans, which resulted in the modern methods of immunization and ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, modeled after the delivery of antitoxin in the 1925 serum run to Nome; the success of animal studies in producing the diphtheria antitoxin has been attributed as a cause for the decline of the early 20th-century opposition to animal research in the United States. Subsequent research in model organisms led to further medical advances, such as Frederick Banting's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with diabetes; this led to the 1922 discovery of insulin and its use in treating diabetes, which had meant death. John Cade's research in guinea pigs discovered the anticonvulsant properties of lithium salts, which revolutionized the treatment of bipolar disorder, replacing the previous treatments of lobotomy or electroconvulsive therapy.
Modern general anaesthetics, such as halothane and related compounds, were developed through studies on model organisms, are necessary for modern, complex surgical operations. In the 1940s, Jonas Salk used rhesus monkey studies to isolate the most virulent forms of the polio virus, which led to his creation of a polio vaccine; the vaccine, made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years. Albert Sabin improved the vaccine by passing the polio virus through animal hosts, including monkeys, it has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but among animals."Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques, the heart-lung machine and the whooping cough vaccine.
Treatments for animal diseases have been developed, including for rabies, anthrax
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. A few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, are present in most of its habitats. Bacteria inhabit soil, acidic hot springs, radioactive waste, the deep portions of Earth's crust. Bacteria live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, only about half of the bacterial phyla have species that can be grown in the laboratory; the study of bacteria is known as a branch of microbiology. There are 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants and animals. Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere.
The nutrient cycle includes the decomposition of dead bodies. In the biological communities surrounding hydrothermal vents and cold seeps, extremophile bacteria provide the nutrients needed to sustain life by converting dissolved compounds, such as hydrogen sulphide and methane, to energy. Data reported by researchers in October 2012 and published in March 2013 suggested that bacteria thrive in the Mariana Trench, with a depth of up to 11 kilometres, is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, "You can find microbes everywhere—they're adaptable to conditions, survive wherever they are."The famous notion that bacterial cells in the human body outnumber human cells by a factor of 10:1 has been debunked. There are 39 trillion bacterial cells in the human microbiota as personified by a "reference" 70 kg male 170 cm tall, whereas there are 30 trillion human cells in the body.
This means that although they do have the upper hand in actual numbers, it is only by 30%, not 900%. The largest number exist in the gut flora, a large number on the skin; the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial in the gut flora. However several species of bacteria are pathogenic and cause infectious diseases, including cholera, anthrax and bubonic plague; the most common fatal bacterial diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year in sub-Saharan Africa. In developed countries, antibiotics are used to treat bacterial infections and are used in farming, making antibiotic resistance a growing problem. In industry, bacteria are important in sewage treatment and the breakdown of oil spills, the production of cheese and yogurt through fermentation, the recovery of gold, palladium and other metals in the mining sector, as well as in biotechnology, the manufacture of antibiotics and other chemicals.
Once regarded as plants constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and harbour membrane-bound organelles. Although the term bacteria traditionally included all prokaryotes, the scientific classification changed after the discovery in the 1990s that prokaryotes consist of two different groups of organisms that evolved from an ancient common ancestor; these evolutionary domains are called Archaea. The word bacteria is the plural of the New Latin bacterium, the latinisation of the Greek βακτήριον, the diminutive of βακτηρία, meaning "staff, cane", because the first ones to be discovered were rod-shaped; the ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, about 4 billion years ago. For about 3 billion years, most organisms were microscopic, bacteria and archaea were the dominant forms of life. Although bacterial fossils exist, such as stromatolites, their lack of distinctive morphology prevents them from being used to examine the history of bacterial evolution, or to date the time of origin of a particular bacterial species.
However, gene sequences can be used to reconstruct the bacterial phylogeny, these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. The most recent common ancestor of bacteria and archaea was a hyperthermophile that lived about 2.5 billion–3.2 billion years ago. Bacteria were involved in the second great evolutionary divergence, that of the archaea and eukaryotes. Here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves related to the Archaea; this involved the engulfment by proto-eukaryotic cells of alphaproteobacterial symbionts to form either mitochondria or hydrogenosomes, which are still found in all known Eukarya. Some eukaryotes that contained mitochondria engulfed cyanobacteria-like organisms, leading to the formation of chloroplasts in algae and plants; this is known as primary endosymbiosis. Bacteria display a wide diversity of sizes, called morphologies.
Bacterial cells are about one-tenth the size of eukaryotic cells
Type three secretion system
Type three secretion system is a protein appendage found in several Gram-negative bacteria. In pathogenic bacteria, the needle-like structure is used as a sensory probe to detect the presence of eukaryotic organisms and secrete proteins that help the bacteria infect them; the secreted effector proteins are secreted directly from the bacterial cell into the eukaryotic cell, where they exert a number of effects that help the pathogen to survive and to escape an immune response. The term Type III secretion system was coined in 1993; this secretion system is distinguished from at least five other secretion systems found in Gram-negative bacteria. Many animal and plant associated bacteria possess similar T3SSs; these T3SSs are similar as a result of divergent evolution and phylogenetic analysis supports a model in which gram-negative bacteria can transfer the T3SS gene cassette horizontally to other species. The most researched T3SSs are from species of Shigella, Escherichia coli, Burkholderia, Chlamydia and the plant pathogens Erwinia and Xanthomonas, the plant symbiont Rhizobium.
The T3SS is composed of 30 different proteins, making it one of the most complex secretion systems. Its structure shows many similarities with bacterial flagella; some of the proteins participating in T3SS share amino-acid sequence homology to flagellar proteins. Some of the bacteria possessing a T3SS have flagella as well and are motile, some do not. Technically speaking, type III secretion is used both for secreting infection-related proteins and flagellar components. However, the term "type III secretion" is used in relation to the infection apparatus; the bacterial flagellum shares a common ancestor with the type III secretion system. T3SSs are essential for the pathogenicity of many pathogenic bacteria. Defects in the T3SS may render a bacterium non-pathogenic, it has been suggested that some non-invasive strains of gram-negative bacteria have lost the T3SS because the energetically costly system is no longer of use. Although traditional antibiotics were effective against these bacteria in the past, antibiotic-resistant strains emerge.
Understanding the way the T3SS works and developing drugs targeting it have become an important goal of many research groups around the world since the late 1990s. The hallmark of T3SS is the needle. Bacterial proteins that need to be secreted pass from the bacterial cytoplasm through the needle directly into the host cytoplasm. Three membranes separate the two cytoplasms: the double membrane of the Gram-negative bacterium and the eukaryotic membrane; the needle provides a smooth passage through those selective and impermeable membranes. A single bacterium can have several hundred needle complexes spread across its membrane, it has been proposed that the needle complex is a universal feature of all T3SSs of pathogenic bacteria. The needle complex starts at the cytoplasm of the bacterium, crosses the two membranes and protrudes from the cell; the part anchored in the membrane is the base of the T3SS. The extracellular part is the needle. A so-called inner rod connects the needle to the base; the needle itself, although the biggest and most prominent part of the T3SS, is made out of many units of a single protein.
The majority of the different T3SS proteins are therefore those that build the base and those that are secreted into the host. As mentioned above, the needle complex shares similarities with bacterial flagella. More the base of the needle complex is structurally similar to the flagellar base; the base is composed of several circular rings and is the first structure, built in a new needle complex. Once the base is completed, it serves as a secretion machine for the outer proteins. Once the whole complex is completed the system switches to secreting proteins that are intended to be delivered into host cells; the needle is presumed to be built from bottom to top. The needle subunit is one of the smallest T3SS proteins, measuring at around 9 kDa. 100−150 subunits comprise each needle. The T3SS needle measures 8 nm in external width, it needs to have a minimal length so that other extracellular bacterial structures do not interfere with secretion. The hole of the needle has a 3 nm diameter. Most folded effector proteins are too large to pass through the needle opening, so most secreted proteins must pass through the needle unfolded, a task carried out by the ATPase at the base of the structure.
The T3SS proteins can be grouped into three categories: Structural proteins: build the base, the inner rod and the needle. Effector proteins: get secreted into the host cell and promote infection / suppress host cell defences. Chaperones: bind effectors in the bacterial cytoplasm, protect them from aggregation and degradation and direct them towards the needle complex. Most T3SS genes are laid out in ope