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42-662: Campylobacterota are a phylum of Gram-negative bacteria . Until the 2021 revision of bacterial taxonomy by the ICSP , the entire phylum was classified within the Proteobacteria (synonym Pseudomonadota ) as the Epsilonproteobacteria and the Desulfurellales . The separation of this phylum from "Proteobacteria" was originally proposed in 2017, using GTDB -based methods. The currently accepted taxonomy

84-459: 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

126-427: 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,

168-665: 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

210-652: 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

252-435: 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

294-742: A primary mode of action as protein synthesis inhibitors , though additional mechanisms are implicated for some specific agents, and/or thorough mechanistic descriptions are as yet unavailable. The inhibition of protein synthesis is mediated through aminoglycosides' energy-dependent, sometimes irreversible binding, to the cytosolic , membrane-associated bacterial ribosome (image at right). (Aminoglycosides first cross bacterial cell walls— lipopolysaccharide in gram-negative bacteria—and cell membranes, where they are actively transported . ) While specific steps in protein synthesis affected may vary somewhat between specific aminoglycoside agents, as can their affinity and degree of binding, aminoglycoside presence in

336-507: A related but distinct chemical structure class often discussed with aminoglycosides, does not induce mRNA misreading and is generally not bactericidal.) It has been proposed that aminoglycoside antibiotics cause oxidation of guanine nucleotides in the bacterial nucleotide pool, and that this contributes to the cytotoxicity of these antibiotics. The incorporation of oxidized guanine nucleotides into DNA could be bactericidal since incomplete repair of closely spaced 8-oxo-2'-deoxyguanosine in

378-519: 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

420-513: Is a stub . You can help Misplaced Pages by expanding it . Gram-negative 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 a protective barrier against numerous antibiotics (including penicillin ), detergents that would normally damage

462-1076: Is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnology Information (NCBI) Desulfurellaceae Hippeaceae Nautiliaceae Nitratiruptoraceae Hydrogenimonadaceae Helicobacteraceae Sulfurovaceae Sulfurimonadaceae Arcobacteraceae Sulfurospirillaceae Sulfurospirillum alkalitolerans Campylobacteraceae Desulfurellaceae Kuever, Rainey & Widdel 2006 Hippeaceae Waite et al. 2020 Nautiliaceae Miroshnichenko et al. 2004 Helicobacteraceae Garrity et al. 2006 Arcobacteraceae Waite et al. 2020 Sulfurospirillaceae Waite et al. 2020 Campylobacteraceae Vandamme & De Ley 1991 Thiovulaceae Waite et al. 2020 Sulfurimonadaceae Waite et al. 2020 Nitratiruptoraceae Waite et al. 2020 Hydrogenimonadaceae Waite et al. 2020 Sulfurovaceae Waite et al. 2020 This Campylobacterota -related article

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504-680: Is necessary to obtain the correct dose. These agents exhibit a post-antibiotic effect in which there is no or very little drug level detectable in blood, but there still seems to be inhibition of bacterial re-growth. This is due to strong, irreversible binding to the ribosome, and remains intracellular long after plasma levels drop, and allows a prolonged dosage interval. Depending on their concentration, they act as bacteriostatic or bactericidal agents. Aminoglycosides are useful primarily in infections involving aerobic , Gram-negative bacteria, such as Pseudomonas , Acinetobacter , and Enterobacter . In addition, some Mycobacteria , including

546-403: 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

588-401: Is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Aminoglycosides can cause inner ear toxicity which can result in sensorineural hearing loss . The incidence of inner ear toxicity varies from 7 to 90%, depending on

630-478: Is the first-in-class aminoglycoside antibiotic . It is derived from Streptomyces griseus and is the earliest modern agent used against tuberculosis . Streptomycin lacks the common 2-deoxystreptamine moiety (image right, below) present in most other members of this class. Other examples of aminoglycosides include the deoxystreptamine-containing agents kanamycin , tobramycin , gentamicin , and neomycin (see below). Aminoglycosides that are derived from bacteria of

672-606: The Streptomyces genus are named with the suffix -mycin , whereas those that are derived from Micromonospora are named with the suffix -micin . However, this nomenclature system is not specific for aminoglycosides, and so appearance of this set of suffixes does not imply common mechanism of action. (For instance, vancomycin , a glycopeptide antibiotic , and erythromycin , a macrolide antibiotic produced by Saccharopolyspora erythraea , along with its synthetic derivatives clarithromycin and azithromycin , all share

714-792: The CDC ), if any, governs the document being written. This is further explained at Gram staining § Orthographic note . Aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ( sugar ). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria. Streptomycin

756-474: 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

798-404: The translated protein product. The subset of aberrant proteins that are incorporated into the bacterial cell membrane may then lead to changes in its permeability and then to "further stimulation of aminoglycoside transport". The amino sugar portion of this class of molecules (e.g., the 2-deoxystreptamine in kanamycins, gentamicins, and tobramycin, see above) are implicated in the association of

840-535: The CFTR protein. Since they are not absorbed from the gut, they are administered intravenously and intramuscularly . Some are used in topical preparations for wounds. Oral administration can be used for gut decontamination (e.g., in hepatic encephalopathy). Tobramycin may be administered in a nebulized form. The recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reevaluate

882-475: The DNA can result in lethal double-strand breaks. Finally, a further "cell-membrane effect" also occurs with aminoglycosides; "functional integrity of the bacterial cell membrane" can be lost, later in time courses of aminoglycoside exposure and transport. There is a significant variability in the relationship between the dose administered and the resultant plasma level in blood. Therapeutic drug monitoring (TDM)

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924-602: The bacteria that cause tuberculosis , are susceptible to aminoglycosides. Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin has been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple-drug-resistant strains. The most frequent use of aminoglycosides is empiric therapy for serious infections such as sepsis , complicated intra-abdominal infections, complicated urinary tract infections, and nosocomial respiratory tract infections. Usually, once cultures of

966-403: The causal organism are grown and their susceptibilities tested, aminoglycosides are discontinued in favor of less toxic antibiotics. As noted, aminoglycosides are mostly ineffective against anaerobic bacteria, fungi, and viruses. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In

1008-412: The cell to overcome the stop codons, insert a random amino acid, and express a full-length protein. The aminoglycoside gentamicin has been used to treat cystic fibrosis (CF) cells in the laboratory to induce them to grow full-length proteins. CF is caused by a mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator ( CFTR ) protein. In approximately 10% of CF cases,

1050-454: The cytosol generally disturbs peptide elongation at the 30S ribosomal subunit, giving rise to inaccurate mRNA translation and therefore biosynthesis of proteins that are truncated, or bear altered amino acid compositions at particular points. Specifically, binding impairs translational proofreading leading to misreading of the RNA message, premature termination, or both, and so to inaccuracy of

1092-420: 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

1134-518: 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

1176-487: 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

1218-1049: 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 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

1260-830: 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

1302-404: The mutation in this gene causes its early termination during translation , leading to the formation of a truncated and non-functional CFTR protein. It is believed that gentamicin distorts the structure of the ribosome-RNA complex, leading to a mis-reading of the termination codon , causing the ribosome to "skip" over the stop sequence and to continue with the normal elongation and production of

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1344-669: The past, the aminoglycosides have been used in conjunction with beta-lactam antibiotics in streptococcal infections for their synergistic effects, in particular in endocarditis . One of the most frequent combinations is ampicillin (a beta-lactam , or penicillin-related antibiotic) and gentamicin. Often, hospital staff refer to this combination as "amp and gent" or more recently called "pen and gent" for penicillin and gentamicin. The interference with mRNA proofreading has been exploited to treat genetic diseases that result from premature stop codons (leading to early termination of protein synthesis and truncated proteins). Aminoglycosides can cause

1386-509: 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

1428-419: 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

1470-488: The relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment makes physicians reluctant to use these compounds in everyday practice. Recent advances in the understanding of the effect of various dosage schedules of aminoglycosides on toxicity have provided a partial solution to this problem, although more research still needs to be done in order to overcome this problem entirely. Aminoglycosides are in pregnancy category D , that is, there

1512-459: 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

1554-506: The small molecule with ribosomal structures that lead to the infidelities in translation (ibid.). Inhibition of ribosomal translocation —i.e., movement of the peptidyl-tRNA from the A- to the P-site—has also been suggested . Recent single-molecule tracking experiments in live E. coli showed an ongoing but slower protein synthesis upon treatment with different aminoglycoside drugs. ( Spectinomycin ,

1596-426: 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

1638-726: The suffixes but have notably different mechanisms of action.) In the following gallery, kanamycin A to netilmicin are examples of the 4,6-disubstituted deoxystreptamine sub-class of aminoglycosides, the neomycins are examples of the 4, 5 -disubstituted sub-class, and streptomycin is an example of a non-deoxystreptamine aminoglycoside. Aminoglycosides display concentration-dependent bactericidal activity against "most gram-negative aerobic and facultative anaerobic bacilli" but not against gram-negative anaerobes and most gram-positive bacteria. They require only short contact time, and are most effective against susceptible bacterial populations that are rapidly multiplying. These activities are attributed to

1680-403: 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

1722-635: The types of antibiotics used, susceptibility of the patient to such antibiotics, and the duration of antibiotic administration. Another serious and disabling side effect of aminoglycoside use is vestibular ototoxicity. This leads to oscillopsia (gaze instability) and balance impairments that impact all aspects of an individual's antigravity function. This loss is permanent and can happen at any dose. Frequent use of aminoglycosides could result in kidney damage (Acute kidney injury), that could lead to chronic kidney disease . Aminoglycosides can exacerbate weakness in patients with myasthenia gravis , and use

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1764-412: The use of these antibacterial agents. This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Current evidence shows that aminoglycosides do retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world. Still,

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