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Enterobacterales

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Gram-negative bacteria are bacteria that, unlike gram-positive bacteria , do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is their cell envelope , which consists of a thin peptidoglycan cell wall sandwiched between an inner ( cytoplasmic ) membrane and an outer membrane . These bacteria are found in all environments that support life on Earth .

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85-500: Enterobacterales is an order of Gram-negative , non-spore forming, facultatively anaerobic , rod-shaped bacteria with the class Gammaproteobacteria . The type genus of this order is Enterobacter . The name Enterobacterales is derived from the Latin term Enterobacter , referring the type genus of the order and the suffix "-ales", an ending used to denote an order. Together, Enterobacterales refers to an order whose nomenclatural type

170-459: A monophyletic clade and that no loss of the outer membrane from any species from this group has occurred. The proteobacteria are a major superphylum of gram-negative bacteria, including E. coli , Salmonella , Shigella , and other Enterobacteriaceae , Pseudomonas , Moraxella , Helicobacter , Stenotrophomonas , Bdellovibrio , acetic acid bacteria , Legionella etc. Other notable groups of gram-negative bacteria include

255-427: A monophyletic taxon (though not a clade ; his definition of monophyly requires a single common ancestor but does not require holophyly , the property that all descendants be encompassed by the taxon ) and refer to the group as a subkingdom "Negibacteria". Bacteria are traditionally classified based on their Gram-staining response into the gram-positive and gram-negative bacteria. Having just one membrane,

340-465: A 2014 study from McGill University in Montreal, Canada which suggests that mice handled by men rather than women showed higher stress levels. Another study in 2016 suggested that gut microbiomes in mice may have an impact upon scientific research. Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for

425-665: A few conserved signature indel (CSI) in the HSP60 ( GroEL ) protein. In addition, a number of bacterial taxa (including Negativicutes , Fusobacteriota , Synergistota , and Elusimicrobiota ) that are either part of the phylum Bacillota (a monoderm group) or branches in its proximity are also found to possess a diderm cell structure. They lack the GroEL signature. The presence of this CSI in all sequenced species of conventional lipopolysaccharide-containing gram-negative bacterial phyla provides evidence that these phyla of bacteria form

510-599: A hypothetical protein, which in most cases are exclusively shared by either all or most members of this order. These CSIs provide a molecular means of demarcating this order from other Gammaproteobacteria and supports the monophyletic nature of the order Enterobacterales. Pasteurellales ( outgroup ) Budviciaceae Morganellaceae Hafniaceae Yersiniaceae Pectobacteriaceae Erwiniaceae Enterobacteriaceae The following genera have been validly published, thus they have "Standing in Nomenclature". The year

595-488: A large, diverse group of species, occupying distinct ecological niches and possessing a variety of biochemical characteristics. Many genera within the order have significant impacts on human activity, such as the pathogenic species Escherichia coli , Salmonella enterica , and Yersinia pestis , as well as agriculture-harming phytopathogens such as members of the genera Dickeya , Pectobacterium , Brenneria , Erwinia and Pantoea . The large number of species as well as

680-591: A local review board called the Institutional Animal Care and Use Committee (IACUC). All laboratory experiments involving living animals are reviewed and approved by this committee. In addition to proving the potential for benefit to human health, minimization of pain and distress, and timely and humane euthanasia, experimenters must justify their protocols based on the principles of Replacement, Reduction and Refinement. "Replacement" refers to efforts to engage alternatives to animal use. This includes

765-406: A lower total neutrophil fraction in the blood , a lower neutrophil enzymatic capacity, lower activity of the complement system , and a different set of pentraxins involved in the inflammatory process ; and lack genes for important components of the immune system, such as IL-8 , IL-37 , TLR10 , ICAM-3 , etc. Laboratory mice reared in specific-pathogen-free (SPF) conditions usually have

850-547: A model for neuronal development by Sydney Brenner in 1963, and has been extensively used in many different contexts since then. C. elegans was the first multicellular organism whose genome was completely sequenced, and as of 2012, the only organism to have its connectome (neuronal "wiring diagram") completed. Arabidopsis thaliana is currently the most popular model plant. Its small stature and short generation time facilitates rapid genetic studies, and many phenotypic and biochemical mutants have been mapped. A. thaliana

935-652: A multitude of species. Some of them cause primarily respiratory problems ( Klebsiella pneumoniae , Legionella pneumophila , Pseudomonas aeruginosa ), primarily urinary problems ( Escherichia coli , Proteus mirabilis , Enterobacter cloacae , Serratia marcescens ), and primarily gastrointestinal problems ( Helicobacter pylori , Salmonella enteritidis , Salmonella typhi ). Gram-negative bacteria associated with hospital-acquired infections include Acinetobacter baumannii , which cause bacteremia , secondary meningitis , and ventilator-associated pneumonia in hospital intensive-care units . Transformation

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1020-666: A nearly transparent body during early development, which provides unique visual access to the animal's internal anatomy during this time period. Zebrafish are used to study development, toxicology and toxicopathology, specific gene function and roles of signaling pathways. Other important model organisms and some of their uses include: T4 phage (viral infection), Tetrahymena thermophila (intracellular processes), maize ( transposons ), hydras ( regeneration and morphogenesis ), cats (neurophysiology), chickens (development), dogs (respiratory and cardiovascular systems), Nothobranchius furzeri (aging), non-human primates such as

1105-435: A number of different observations, including that the gram-positive bacteria are the most sensitive to antibiotics and that the gram-negative bacteria are, in general, resistant to antibiotics, it has been proposed that the outer cell membrane in gram-negative bacteria (diderms) evolved as a protective mechanism against antibiotic selection pressure . Some bacteria such as Deinococcus , which stain gram-positive due to

1190-551: A portal from which to download sequences (DNA, RNA, or protein) or to access functional information on specific genes, for example the sub-cellular localization of the gene product or its physiological role. Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively sedentary , obese and glucose intolerant . This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and exercise . Similarly, there are differences between

1275-401: A protective barrier against numerous antibiotics (including penicillin ), detergents that would normally damage the inner cell membrane, and the antimicrobial enzyme lysozyme produced by animals as part of their innate immune system . Furthermore, the outer leaflet of this membrane contains a complex lipopolysaccharide (LPS) whose lipid A component can trigger a toxic reaction when

1360-588: A rather immature immune system with a deficit of memory T cells . These mice may have limited diversity of the microbiota , which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, herpesviruses ) are activated in humans, but not in SPF mice, with septic complications and may change the resistance to bacterial coinfections . “Dirty” mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in

1445-519: A toxic reaction, resulting in fever, an increased respiratory rate, and low blood pressure . That is why some infections with gram-negative bacteria can lead to life-threatening septic shock . The outer membrane protects the bacteria from several antibiotics , dyes , and detergents that would normally damage either the inner membrane or the cell wall (made of peptidoglycan ). The outer membrane provides these bacteria with resistance to lysozyme and penicillin . The periplasmic space (space between

1530-468: A unicellular green alga with well-studied genetics, is used to study photosynthesis and motility . C. reinhardtii has many known and mapped mutants and expressed sequence tags, and there are advanced methods for genetic transformation and selection of genes. Dictyostelium discoideum is used in molecular biology and genetics , and is studied as an example of cell communication , differentiation , and programmed cell death . Among invertebrates,

1615-506: A wide variety of experimental techniques and goals from many different levels of biology—from ecology , behavior and biomechanics , down to the tiny functional scale of individual tissues , organelles and proteins . Inquiries about the DNA of organisms are classed as genetic models (with short generation times, such as the fruitfly and nematode worm), experimental models, and genomic parsimony models, investigating pivotal position in

1700-548: A wider assortment of lineages on the tree of life . The primary reason for the use of model organisms in research is the evolutionary principle that all organisms share some degree of relatedness and genetic similarity due to common ancestry . The study of taxonomic human relatives, then, can provide a great deal of information about mechanism and disease within the human body that can be useful in medicine. Various phylogenetic trees for vertebrates have been constructed using comparative proteomics , genetics, genomics as well as

1785-412: Is Escherichia coli ( E. coli ), which has been intensively investigated for over 60 years. It is a common, gram-negative gut bacterium which can be grown and cultured easily and inexpensively in a laboratory setting. It is the most widely used organism in molecular genetics , and is an important species in the fields of biotechnology and microbiology , where it has served as the host organism for

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1870-439: Is difficult to build an animal model that perfectly reproduces the symptoms of depression in patients. Depression, as other mental disorders , consists of endophenotypes that can be reproduced independently and evaluated in animals. An ideal animal model offers an opportunity to understand molecular , genetic and epigenetic factors that may lead to depression. By using animal models, the underlying molecular alterations and

1955-509: Is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution . Research using animal models has been central to most of the achievements of modern medicine. It has contributed most of the basic knowledge in fields such as human physiology and biochemistry , and has played significant roles in fields such as neuroscience and infectious disease . The results have included

2040-645: Is no substitute for a living organism when studying complex interactions in disease pathology or treatments. Debate about the ethical use of animals in research dates at least as far back as 1822 when the British Parliament under pressure from British and Indian intellectuals enacted the first law for animal protection preventing cruelty to cattle. This was followed by the Cruelty to Animals Act of 1835 and 1849, which criminalized ill-treating, over-driving, and torturing animals. In 1876, under pressure from

2125-431: Is no useful in vitro model system available. Model organisms are drawn from all three domains of life, as well as viruses . One of the first model systems for molecular biology was the bacterium Escherichia coli ( E. coli ), a common constituent of the human digestive system. The mouse ( Mus musculus ) has been used extensively as a model organism and is associated with many important biological discoveries of

2210-403: Is one of three processes for horizontal gene transfer , in which exogenous genetic material passes from one bacterium to another, the other two being conjugation (transfer of genetic material between two bacterial cells in direct contact) and transduction (injection of foreign DNA by a bacteriophage virus into the host bacterium). In transformation, the genetic material passes through

2295-420: Is particularly useful as a toxicology model, and as a neurological model and source of primary cell cultures, owing to the larger size of organs and suborganellar structures relative to the mouse, while eggs and embryos from Xenopus tropicalis and Xenopus laevis (African clawed frog) are used in developmental biology, cell biology, toxicology, and neuroscience. Likewise, the zebrafish ( Danio rerio ) has

2380-479: Is similar to a human condition. These test conditions are often termed as animal models of disease . The use of animal models allows researchers to investigate disease states in ways which would be inaccessible in a human patient, performing procedures on the non-human animal that imply a level of harm that would not be considered ethical to inflict on a human. The best models of disease are similar in etiology (mechanism of cause) and phenotype (signs and symptoms) to

2465-496: Is studied, again, because it is easy to grow for an animal, has various visible congenital traits and has a polytene (giant) chromosome in its salivary glands that can be examined under a light microscope. The roundworm Caenorhabditis elegans is studied because it has very defined development patterns involving fixed numbers of cells, and it can be rapidly assayed for abnormalities. Animal models serving in research may have an existing, inbred or induced disease or injury that

2550-550: Is the genus Enterobacter . Enterobacterales was proposed in 2005 under the name "Enterobacteriales". However, the name "Enterobacteriales" was not validated according to the rules of the International Code of Nomenclature of Prokaryotes , thus it lacked standing in nomenclature, so the name was written in parentheses. "Enterobacteriales" was a monotypic order , containing only the family Enterobacteriaceae , and shared its type genus Escherichia . The order contained

2635-477: Is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there is no useful in vitro model system available. Models are those organisms with a wealth of biological data that make them attractive to study as examples for other species and/or natural phenomena that are more difficult to study directly. Continual research on these organisms focuses on

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2720-589: The CDC ), if any, governs the document being written. This is further explained at Gram staining § Orthographic note . Model organism A model organism is a non-human species that is 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 widely used to research human disease when human experimentation would be unfeasible or unethical . This strategy

2805-515: The National Anti-Vivisection Society , the Cruelty to Animals Act was amended to include regulations governing the use of animals in research. This new act stipulated that 1) experiments must be proven absolutely necessary for instruction, or to save or prolong human life; 2) animals must be properly anesthetized; and 3) animals must be killed as soon as the experiment is over. Today, these three principles are central to

2890-474: The cyanobacteria , spirochaetes , green sulfur , and green non-sulfur bacteria . Medically-relevant gram-negative diplococci include the four types that cause a sexually transmitted disease ( Neisseria gonorrhoeae ), a meningitis ( Neisseria meningitidis ), and respiratory symptoms ( Moraxella catarrhalis , A coccobacillus Haemophilus influenzae is another medically relevant coccal type. Medically relevant gram-negative bacilli include

2975-410: The fruit fly Drosophila melanogaster is famous as the subject of genetics experiments by Thomas Hunt Morgan and others. They are easily raised in the lab, with rapid generations, high fecundity , few chromosomes , and easily induced observable mutations. The nematode Caenorhabditis elegans is used for understanding the genetic control of development and physiology. It was first proposed as

3060-622: The rhesus macaque and chimpanzee ( hepatitis , HIV , Parkinson's disease , cognition , and vaccines ), and ferrets ( SARS-CoV-2 ) The organisms below have become model organisms because they facilitate the study of certain characters or because of their genetic accessibility. For example, E. coli was one of the first organisms for which genetic techniques such as transformation or genetic manipulation has been developed. The genomes of all model species have been sequenced , including their mitochondrial / chloroplast genomes. Model organism databases exist to provide researchers with

3145-561: The 20th and 21st centuries. Other examples include baker's yeast ( Saccharomyces cerevisiae ), the T4 phage virus, the fruit fly Drosophila melanogaster , the flowering plant Arabidopsis thaliana , and guinea pigs ( Cavia porcellus ). Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). Disease models are divided into three categories: homologous animals have

3230-549: The DBA ("dilute, brown and non-agouti") 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 then in humans, which resulted in

3315-622: The United States by 1965. 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 also among animals." Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

3400-430: 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 (with John Macleod ) and its use in treating diabetes, which had previously meant death. John Cade 's research in guinea pigs discovered

3485-438: 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 also developed through studies on model organisms, and are necessary for modern, complex surgical operations. In the 1940s, Jonas Salk used rhesus monkey studies to isolate

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3570-765: The bacteria are lysed by immune cells. This reaction may lead to septic shock , resulting in low blood pressure , respiratory failure , reduced oxygen delivery , and lactic acidosis . Several classes of antibiotics have been developed to target gram-negative bacteria, including aminopenicillins , ureidopenicillins , cephalosporins , beta-lactam - betalactamase inhibitor combinations (such as piperacillin-tazobactam ), folate antagonists , quinolones , and carbapenems . Many of these antibiotics also cover gram-positive bacteria. The antibiotics that specifically target gram-negative organisms include aminoglycosides , monobactams (such as aztreonam ), and ciprofloxacin . Conventional gram-negative (LPS-diderm) bacteria display

3655-457: The basic knowledge in fields such as human physiology and biochemistry , and 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 , and have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan 's work with the fruit fly Drosophila melanogaster identified chromosomes as

3740-420: The causal relationship between genetic or environmental alterations and depression can be examined, which would afford a better insight into pathology of depression. In addition, animal models of depression are indispensable for identifying novel therapies for depression. Model organisms are drawn from all three domains of life, as well as viruses . The most widely studied prokaryotic model organism

3825-420: The diderm bacteria in which the outer cell membrane is made up of mycolic acid (e. g. Mycobacterium ). The conventional LPS- diderm group of gram-negative bacteria (e.g., Pseudomonadota , Aquificota , Chlamydiota , Bacteroidota , Chlorobiota , " Cyanobacteria ", Fibrobacterota , Verrucomicrobiota , Planctomycetota , Spirochaetota , Acidobacteriota ; " Hydrobacteria ") are uniquely identified by

3910-533: The evolutionary tree. Historically, model organisms include a handful of species with extensive genomic research data, such as the NIH model organisms. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. This usually will include characteristics such as short life-cycle , techniques for genetic manipulation ( inbred strains, stem cell lines, and methods of transformation ) and non-specialist living requirements. Sometimes,

3995-455: 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, and 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 most of the achievements of modern medicine. It has contributed most of

4080-518: The following characteristics : Along with cell shape, Gram staining is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria. Historically , the kingdom Monera was divided into four divisions based on Gram staining: Firmacutes (+), Gracillicutes (−), Mollicutes (0) and Mendocutes (var.). Since 1987, the monophyly of the gram-negative bacteria has been disproven with molecular studies . However some authors, such as Cavalier-Smith still treat them as

4165-550: The genome arrangement facilitates the sequencing of the model organism's genome, for example, by being very compact or having a low proportion of junk DNA (e.g. yeast , arabidopsis , or pufferfish ). When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time , accessibility, manipulation, genetics, conservation of mechanisms, and potential economic benefit. As comparative molecular biology has become more common, some researchers have sought model organisms from

4250-420: The genus was proposed is listed in parentheses after the genus name. Gram-negative bacteria Within this category, notable species include the model organism Escherichia coli , along with various pathogenic bacteria , such as Pseudomonas aeruginosa , Chlamydia trachomatis , and Yersinia pestis . They pose significant challenges in the medical field due to their outer membrane, which acts as

4335-430: The geochemical and fossil record. These estimations tell us that humans and chimpanzees last shared a common ancestor about 6 million years ago (mya). As our closest relatives, chimpanzees have a lot of potential to tell us about mechanisms of disease (and what genes may be responsible for human intelligence). However, chimpanzees are rarely used in research and are protected from highly invasive procedures. Rodents are

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4420-487: The gram-positive bacteria are also known as monoderm bacteria , while gram-negative bacteria, having two membranes, are also known as diderm bacteria . It was traditionally thought that the groups represent lineages, i.e., the extra membrane only evolved once, such that gram-negative bacteria are more closely related to one another than to any gram-positive bacteria. While this is often true, the classification system breaks down in some cases, with lineage groupings not matching

4505-563: The guidance of animal models. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and is used with the aim of solving medical problems such as Alzheimer's disease, AIDS, multiple sclerosis, spinal cord injury, many headaches, and other conditions in which there

4590-540: The heart-lung machine, antibiotics , and the whooping cough vaccine. In researching human disease , model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species of the model organism is usually chosen so that it reacts to disease or its treatment in a way that resembles human physiology , even though care must be taken when generalizing from one organism to another. However, many drugs, treatments and cures for human diseases are developed in part with

4675-428: The heart-lung machine, antibiotics , and the whooping cough vaccine. Treatments for animal diseases have also been developed, including for rabies , anthrax , glanders , feline immunodeficiency virus (FIV), tuberculosis , Texas cattle fever, classical swine fever (hog cholera), heartworm , and other parasitic infections . Animal experimentation continues to be required for biomedical research, and

4760-412: The host cells for propagation. In eukaryotes , several yeasts, particularly Saccharomyces cerevisiae ("baker's" or "budding" yeast), have been widely used in genetics and cell biology , largely because they are quick and easy to grow. The cell cycle in a simple yeast is very similar to the cell cycle in humans and is regulated by homologous proteins. The fruit fly Drosophila melanogaster

4845-904: The human equivalent. However complex human diseases can often be better understood in a simplified system in which individual parts of the disease process are isolated and examined. For instance, behavioral analogues of anxiety or pain in laboratory animals can be used to screen and test new drugs for the treatment of these conditions in humans. A 2000 study found that animal models concorded (coincided on true positives and false negatives) with human toxicity in 71% of cases, with 63% for nonrodents alone and 43% for rodents alone. In 1987, Davidson et al. suggested that selection of an animal model for research be based on nine considerations. These include 1) appropriateness as an analog, 2) transferability of information, 3) genetic uniformity of organisms, where applicable, 4) background knowledge of biological properties, 5) cost and availability, 6) generalizability of

4930-621: The immune systems of model organisms and humans that lead to significantly altered responses to stimuli, although the underlying principles of genome function may be the same. The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development. Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience. Mice differ from humans in several immune properties: mice are more resistant to some toxins than humans; have

5015-830: The intervening medium, and uptake is completely dependent on the recipient bacterium. As of 2014 about 80 species of bacteria were known to be capable of transformation, about evenly divided between gram-positive and gram-negative bacteria; the number might be an overestimate since several of the reports are supported by single papers. Transformation has been studied in medically important gram-negative bacteria species such as Helicobacter pylori , Legionella pneumophila , Neisseria meningitidis , Neisseria gonorrhoeae , Haemophilus influenzae and Vibrio cholerae . It has also been studied in gram-negative species found in soil such as Pseudomonas stutzeri , Acinetobacter baylyi , and gram-negative plant pathogens such as Ralstonia solanacearum and Xylella fastidiosa . One of

5100-408: The laboratory. Some examples include: Spontaneous models refer to diseases that are analogous to human conditions that occur naturally in the animal being studied. These models are rare, but informative. Negative models essentially refer to control animals, which are useful for validating an experimental result. Orphan models refer to diseases for which there is no human analog and occur exclusively in

5185-598: The laws and guidelines governing the use of animals and research. In the U.S., the Animal Welfare Act of 1970 (see also Laboratory Animal Welfare Act ) set standards for animal use and care in research. This law is enforced by APHIS's Animal Care program. In academic settings in which NIH funding is used for animal research, institutions are governed by the NIH Office of Laboratory Animal Welfare (OLAW). At each site, OLAW guidelines and standards are upheld by

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5270-412: The majority of work with recombinant DNA . Simple model eukaryotes include baker's yeast ( Saccharomyces cerevisiae ) and fission yeast ( Schizosaccharomyces pombe ), both of which share many characters with higher cells, including those of humans. For instance, many cell division genes that are critical for the development of cancer have been discovered in yeast. Chlamydomonas reinhardtii ,

5355-479: The modern methods of immunization and largely ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, which is modeled after the delivery of antitoxin in the 1925 serum run to Nome . The success of animal studies in producing the diphtheria antitoxin has also been attributed as a cause for the decline of the early 20th-century opposition to animal research in

5440-550: The most common animal models. Phylogenetic trees estimate that humans and rodents last shared a common ancestor ~80-100mya. Despite this distant split, humans and rodents have far more similarities than they do differences. This is due to the relative stability of large portions of the genome, making the use of vertebrate animals particularly productive. Genomic data is used to make close comparisons between species and determine relatedness. Humans share about 99% of their genome with chimpanzees (98.7% with bonobos) and over 90% with

5525-497: The most virulent forms of the polio virus, which led to his creation of a polio vaccine . The vaccine, which was 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; the Sabin vaccine was produced for mass consumption in 1963, and had virtually eradicated polio in

5610-436: The mouse. With so much of the genome conserved across species, it is relatively impressive that the differences between humans and mice can be accounted for in approximately six thousand genes (of ~30,000 total). Scientists have been able to take advantage of these similarities in generating experimental and predictive models of human disease. There are many model organisms. One of the first model systems for molecular biology

5695-463: The near- eradication of polio and the development of organ transplantation , and 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, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". Research in model organisms led to further medical advances, such as

5780-511: The order Enterobacterales contains 7 validly published families ( Budviciaceae , Enterobacteriaceae , Erwiniaceae , Hafniaceae , Morganellaceae , Pectobacteriaceae and Yersiniaceae ). Analyses of genome sequences from Enterobacterales species identified five conserved signature indels (CSIs) for this order in the proteins peptide ABC transporter permease, elongation factor P-like protein YeiP, L-arabinose isomerase , pyrophosphatase , and

5865-454: The overwhelming majority of studies, while the human population is heterogeneous, pointing to the importance of studies in interstrain hybrid, outbred , and nonlinear mice. Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include

5950-509: The peri-plasmic space. Other classes of drugs that have gram negative spectrum include cephalosporins , monobactams ( aztreonam ), aminoglycosides, quinolones , macrolides , chloramphenicol , folate antagonists , and carbapenems . The adjectives gram-positive and gram-negative derive from the surname of Hans Christian Gram , a Danish bacteriologist; as eponymous adjectives , their initial letter can be either capital G or lower-case g , depending on which style guide (e.g., that of

6035-419: The presence of a thick peptidoglycan layer, but also possess an outer cell membrane are suggested as intermediates in the transition between monoderm (gram-positive) and diderm (gram-negative) bacteria. The diderm bacteria can also be further differentiated between simple diderms lacking lipopolysaccharide (LPS); the archetypical diderm bacteria, in which the outer cell membrane contains lipopolysaccharide; and

6120-451: The production of the diphtheria antitoxin and the 1922 discovery of insulin and its use in treating diabetes, which had previously meant death. Modern general anaesthetics such as halothane were also developed through studies on model organisms, and are necessary for modern, complex surgical operations. Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques,

6205-494: The range of different biochemical characteristics made describing the order and its subgroups extremely difficult. The assignment and classification of this order was largely based on 16S rRNA genome sequences, which is known to have low discriminatory power and yield different results depending on the algorithm and organism strain used. In addition, these analyses have shown that 'Enterobacteriales' exhibited polyphyletic branching, with distinct subgroups. In 2016, "Enterobacteriales"

6290-505: The results, 7) ease of and adaptability to experimental manipulation, 8) ecological consequences, and 9) ethical implications. Animal models can be classified as homologous, isomorphic or predictive. Animal models can also be more broadly classified into four categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan. Experimental models are most common. These refer to models of disease that resemble human conditions in phenotype or response to treatment but are induced artificially in

6375-476: The same causes, symptoms and treatment options as would humans who have the same disease, isomorphic animals share the same symptoms and treatments, and 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 (384–322 BCE) and Erasistratus (304–258 BCE) among

6460-459: The several unique characteristics of gram-negative bacteria is the structure of the bacterial outer membrane . The outer leaflet of this membrane contains lipopolysaccharide (LPS), whose lipid A portion acts as an endotoxin . If gram-negative bacteria enter the circulatory system , LPS can trigger an innate immune response , activating the immune system and producing cytokines (hormonal regulators). This leads to inflammation and can cause

6545-469: The species studied. The increase in knowledge of the genomes of non-human primates and other mammals that are genetically close to humans is allowing the production of genetically engineered animal tissues, organs and even animal species which express human diseases, providing a more robust model of human diseases in an animal model. Animal models observed in the sciences of psychology and sociology are often termed animal models of behavior . It

6630-426: The staining result. Thus, Gram staining cannot be reliably used to assess familial relationships of bacteria. Nevertheless, staining often gives reliable information about the composition of the cell membrane, distinguishing between the presence or absence of an outer lipid membrane . Of these two structurally distinct groups of prokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon

6715-581: The study of disease. Cell culture, or in vitro studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible pluripotent stem cells can also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies. Many biomedical researchers argue that there

6800-403: The two cell membranes) also contains enzymes which break down or modify antibiotics. Drugs commonly used to treat gram negative infections include amino, carboxy and ureido penicillins ( ampicillin , amoxicillin , pipercillin , ticarcillin ). These drugs may be combined with beta-lactamase inhibitors to combat the presence of enzymes that can digest these drugs (known as beta-lactamases ) in

6885-491: The use of computer models, non-living tissues and cells, and replacement of “higher-order” animals (primates and mammals) with “lower” order animals (e.g. cold-blooded animals, invertebrates) wherever possible. "Reduction" refers to efforts to minimize number of animals used during the course of an experiment, as well as prevention of unnecessary replication of previous experiments. To satisfy this requirement, mathematical calculations of statistical power are employed to determine

6970-483: The vector of inheritance for genes. Drosophila became one of the first, and for some time the most widely used, model organisms, and Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science". D. melanogaster remains one of the most widely 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

7055-637: Was proposed to be reclassified as Enterobacterales, and the type genus changed to Enterobacter in accordance with the International Code of Nomenclature of Prokaryotes. In addition, several new families within the order Enterobacterales were proposed, consisting of species that were formerly members of the family Enterobacteriaceae based on groupings found in phylogenetic trees constructed based on conserved genomes, 16S rRNA sequences and multi-locus sequence analysis as well as independent molecular markers ( conserved signature indels ). As of 2021,

7140-417: Was the bacterium Escherichia coli , a common constituent of the human digestive system. Several of the bacterial viruses ( bacteriophage ) that infect E. coli also have been very useful for the study of gene structure and gene regulation (e.g. phages Lambda and T4 ). However, it is debated whether bacteriophages should be classified as organisms, because they lack metabolism and depend on functions of

7225-569: Was the first plant to have its genome sequenced . Among vertebrates , guinea pigs ( Cavia porcellus ) were used by Robert Koch and other early bacteriologists as a host for bacterial infections, becoming a byword for "laboratory animal", but are less commonly used today. The classic model vertebrate is currently the mouse ( Mus musculus ). Many inbred strains exist, as well as lines selected for particular traits, often of medical interest, e.g. body size, obesity, muscularity, and voluntary wheel-running behavior. The rat ( Rattus norvegicus )

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