Gram-negative bacteria arebacteria that, unlikegram-positive bacteria, do not retain thecrystal violet stain used in theGram staining method of bacterial differentiation.[1] Their defining characteristic is that theircell envelope consists of a thinpeptidoglycancell wall sandwiched between an inner (cytoplasmic)membrane and anouter membrane.[2] These bacteria are found in all environments that support life onEarth.
Within this category, notable species include themodel organismEscherichia coli, along with variouspathogenic bacteria, such asPseudomonas aeruginosa,Chlamydia trachomatis, andYersinia pestis. They pose significant challenges in the medical field due to their outer membrane, which acts as a protective barrier against numerousantibiotics (includingpenicillin),detergents that would normally damage the inner cell membrane, and theantimicrobial enzymelysozyme produced by animals as part of theirinnate immune system. Furthermore, the outerleaflet of this membrane contains a complexlipopolysaccharide (LPS) whoselipid A component can trigger a toxic reaction when the bacteria arelysed by immune cells. This reaction may lead toseptic shock, resulting inlow blood pressure,respiratory failure,reduced oxygen delivery, andlactic acidosis.[3]
Severalclasses of antibiotics have been developed to target gram-negative bacteria, includingaminopenicillins,ureidopenicillins,cephalosporins,beta-lactam-betalactamase inhibitor combinations (such aspiperacillin-tazobactam),folate antagonists,quinolones, andcarbapenems. Many of these antibiotics also cover gram-positive bacteria. The antibiotics that specifically target gram-negative organisms includeaminoglycosides,monobactams (such asaztreonam), andciprofloxacin.
Conventional gram-negative (LPS-diderm) bacteria displaythe following characteristics:[citation needed]
However, the LPS-diderm group (corresponding to kingdomPseudomonadati, formerly 'Hydrobacteria') is not the only type of bacteria that stain negative.[4]Mycobacterium (or rather most ofMycobacteriales), which does not belong in the group, have independently evolved an outer cell membrane, with a cell wall made ofmycolic acid.[5] This gives it very different structure and features.[6][7][8][9]
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 kingdomMonera was divided into fourdivisions based on Gram staining:Firmicutes (+),Gracillicutes (−),Mollicutes (0) andMendocutes (var.).[10]Since 1987, themonophyly of the gram-negative bacteria has beendisproven withmolecular studies.[11] However some authors, such asCavalier-Smith still treat them as amonophyletictaxon (though not aclade; his definition ofmonophyly requires a single common ancestor but does not requireholophyly, the property that all descendants be encompassed by thetaxon) and refer to the group as asubkingdom "Negibacteria".[12]
Current knowledge divides the gram-negatives into two large groups and some straddlers. The more "conventional" Gram-negatives with an LPS outer membrane do share a common ancestor and are grouped in kingdomPseudomonadati.[4] The less conventional ones are, as mentioned above, the orderMycobacteriales, have amycolic acid cell wall and an outer membrane.[5] The kingdom and the order are each monophyletic (or rather, not holyphyletic), but the "LPS-diderm" and "mycolic-diderm" groups are not, because some bacteria in the kingdom and the order do not, in fact, stain gram negative. They will be discussed in the next section.
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Bacteria are traditionally classified based on theirGram-staining response into thegram-positive and gram-negative bacteria. Having just one membrane, the gram-positive bacteria are also known asmonoderm bacteria, while gram-negative bacteria, having two membranes, are also known asdiderm 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 the staining result.[13][14][6][7] 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 anouter lipid membrane.[13][15]
Of these two structurally distinct groups ofprokaryotic organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations, including that the gram-positive bacteria are the most sensitive toantibiotics 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 antibioticselection pressure.[13][14][15][8] Some bacteria such asDeinococcus, which stain gram-positive due to the presence of a thickpeptidoglycan layer, but also possess an outer cell membrane are suggested as intermediates in the transition between monoderm (gram-positive) and diderm (gram-negative) bacteria.[13][8]
The conventional LPS-diderm group of gram-negative bacteria (e.g.,Pseudomonadota,Aquificota,Chlamydiota,Bacteroidota,Chlorobiota, "Cyanobacteria",Fibrobacterota,Verrucomicrobiota,Planctomycetota,Spirochaetota,Acidobacteriota) are uniquely identified by a fewconserved signature indel (CSI) in theHSP60 (GroEL) protein. 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 amonophyleticclade and that no loss of the outer membrane from any species from this group has occurred.[8] They have accordingly been assigned a kingdomPseudomonadati (formerly "Hydrobacteria").[4]
The difficulty lies in the other taxa that also have a diderm structure.
Theproteobacteria are a major superphylum of gram-negative bacteria, includingE. coli,Salmonella,Shigella, and otherEnterobacteriaceae,Pseudomonas,Moraxella,Helicobacter,Stenotrophomonas,Bdellovibrio,acetic acid bacteria,Legionella etc. Other notable groups of gram-negative bacteria include thecyanobacteria,spirochaetes, andgreen sulfur bacteria.[17][18][19]
Medically-relevant gram-negativediplococci include the four types that cause asexually transmitted disease (Neisseria gonorrhoeae[20]), ameningitis (Neisseria meningitidis[21]), and respiratory symptoms (Moraxella catarrhalis,[22] AcoccobacillusHaemophilus influenzae is another medically relevant coccal type.[23]
Medically relevant gram-negativebacilli include 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).[citation needed]
Gram-negative bacteria associated withhospital-acquired infections includeAcinetobacter baumannii, which causebacteremia, secondarymeningitis, andventilator-associated pneumonia in hospitalintensive-care units.
Transformation is one of three processes forhorizontal gene transfer, in which exogenous genetic material passes from onebacterium to another, the other two beingconjugation (transfer ofgenetic material between two bacterial cells in direct contact) andtransduction (injection of foreign DNA by abacteriophage virus into the host bacterium).[24][25] In transformation, thegenetic material passes through the intervening medium, and uptake is completely dependent on the recipient bacterium.[24]
As of 2014 about 80 species of bacteria were known to be capable of transformation, about evenly divided betweengram-positive and gram-negative bacteria; the number might be an overestimate since several of the reports are supported by single papers.[24] Transformation has been studied in medically important gram-negative bacteria species such asHelicobacter pylori,Legionella pneumophila,Neisseria meningitidis,Neisseria gonorrhoeae,Haemophilus influenzae andVibrio cholerae.[26] It has also been studied in gram-negative species found in soil such asPseudomonas stutzeri,Acinetobacter baylyi, and gram-negative plant pathogens such asRalstonia solanacearum andXylella fastidiosa.[26]
One of the several unique characteristics of gram-negative bacteria is the structure of thebacterial outer membrane. The outer leaflet of this membrane containslipopolysaccharide (LPS), whoselipid A portion acts as anendotoxin.[1] If gram-negative bacteria enter thecirculatory system, LPS can trigger aninnate immune response, activating theimmune system and producingcytokines (hormonal regulators). This leads toinflammation and can cause a toxic reaction, resulting in fever, an increased respiratory rate, andlow blood pressure. That is why some infections with gram-negative bacteria can lead to life-threateningseptic shock.[3]
The outer membrane protects the bacteria from severalantibiotics,dyes, anddetergents that would normally damage either the inner membrane or the cell wall (made ofpeptidoglycan). The outer membrane provides these bacteria with resistance tolysozyme andpenicillin. Theperiplasmic space (space between the two cell membranes) also containsenzymes 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 withbeta-lactamase inhibitors to combat the presence of enzymes that can digest these drugs (known asbeta-lactamases) in the peri-plasmic space. Other classes of drugs that have gram negative spectrum includecephalosporins,monobactams (aztreonam), aminoglycosides,quinolones,macrolides,chloramphenicol,folate antagonists, andcarbapenems.[27]
The adjectivesgram-positive andgram-negative derive from the surname ofHans Christian Gram, a Danish bacteriologist; aseponymous adjectives, their initial letter can be either capitalG or lower-caseg, depending on whichstyle guide (e.g., that of theCDC), if any, governs the document being written.[28] This is further explained atGram staining § Orthographic note.
This article incorporatespublic domain material fromScience Primer.NCBI. Archived fromthe original on 2009-12-08.Mycolic acids are important constituents of the cell envelopes of most members.
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