Gram-negative bacteria: Difference between revisions
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{{Short description|Group of bacteria that do not retain the Gram stain used in bacterial differentiation}} | {{Short description|Group of bacteria that do not retain the Gram stain used in bacterial differentiation}} | ||
[[File:Pseudomonas aeruginosa Gram.jpg|thumb|Microscopic image of | [[File:Pseudomonas aeruginosa Gram.jpg|thumb|Microscopic image of Gram-negative ''[[Pseudomonas aeruginosa]]'' bacteria (pink-red rods)]]<!--no px size to allow auto-sizing per user--> | ||
'''Gram-negative bacteria''' are [[bacteria]] that, unlike [[ | '''Gram-negative bacteria''' are [[bacteria]] that, unlike [[Gram-positive bacteria]], do not retain the [[Crystal violet|crystal violet stain]] used in the [[Gram stain]]ing method of bacterial differentiation.<ref name=Baron>{{cite book| pmid = 21413343| vauthors = Baron S, Salton MR, Kim KS| chapter = Structure| title = Medical Microbiology| editor = Baron S| edition = 4th| publisher = University of Texas Medical Branch at Galveston| year = 1996| chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK8477/| isbn = 978-0-9631172-1-2| access-date = 2021-08-18| archive-date = 2021-07-06| archive-url = https://web.archive.org/web/20210706013613/https://www.ncbi.nlm.nih.gov/books/NBK8477/| url-status = live}}</ref> Their defining characteristic is that their [[cell envelope]] consists of a thin [[peptidoglycan]] [[gram-negative cell wall|cell wall]] sandwiched between an inner ([[Cytoplasm|cytoplasmic]]) [[Cell membrane|membrane]] and an [[Bacterial outer membrane|outer membrane]].<ref>{{Cite journal |last1=Silhavy |first1=T. J. |last2=Kahne |first2=D. |last3=Walker |first3=S. |date=2010-05-01 |title=The Bacterial Cell Envelope |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=2 |issue=5 |article-number=a000414 |doi=10.1101/cshperspect.a000414 |issn=1943-0264 |pmc=2857177 |pmid=20452953}}</ref> These bacteria are found in all environments that support life on [[Earth]]. | ||
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 [[Antibiotic|antibiotics]] (including [[penicillin]]), [[Detergent|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 [[Lipid_bilayer|leaflet]] of this membrane contains a complex [[lipopolysaccharide]] (LPS) whose [[lipid A]] component can trigger a toxic reaction when the bacteria are [[Lysis|lysed]] by immune cells. This reaction may lead to [[septic shock]], resulting in [[hypotension|low blood pressure]], [[respiratory failure]], [[hypoxia (medical)|reduced oxygen delivery]], and [[lactic acidosis]].<ref name="ww.ncbi.nlm.nih.gov">{{cite book |pmid=21413321 |last1=Pelletier |first1=Lawrence L. |editor=Baron S |title=Medical Microbiology |date=1996 |publisher=University of Texas Medical Branch at Galveston |isbn=978-0-9631172-1-2 |edition=4th |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8290/ |chapter=Microbiology of the Circulatory System |access-date=2021-05-12 |archive-date=2022-04-13 |archive-url=https://web.archive.org/web/20220413142416/https://www.ncbi.nlm.nih.gov/books/NBK8290/ |url-status=live }}</ref> | 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 [[Antibiotic|antibiotics]] (including [[penicillin]]), [[Detergent|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 [[Lipid_bilayer|leaflet]] of this membrane contains a complex [[lipopolysaccharide]] (LPS) whose [[lipid A]] component can trigger a toxic reaction when the bacteria are [[Lysis|lysed]] by immune cells. This reaction may lead to [[septic shock]], resulting in [[hypotension|low blood pressure]], [[respiratory failure]], [[hypoxia (medical)|reduced oxygen delivery]], and [[lactic acidosis]].<ref name="ww.ncbi.nlm.nih.gov">{{cite book |pmid=21413321 |last1=Pelletier |first1=Lawrence L. |editor=Baron S |title=Medical Microbiology |date=1996 |publisher=University of Texas Medical Branch at Galveston |isbn=978-0-9631172-1-2 |edition=4th |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK8290/ |chapter=Microbiology of the Circulatory System |access-date=2021-05-12 |archive-date=2022-04-13 |archive-url=https://web.archive.org/web/20220413142416/https://www.ncbi.nlm.nih.gov/books/NBK8290/ |url-status=live }}</ref> | ||
Several [[Antibiotics#Classes|classes of antibiotic]]s have been developed to target | Several [[Antibiotics#Classes|classes of antibiotic]]s have been developed to target Gram-negative bacteria, including [[aminopenicillin]]s, [[ureidopenicillin]]s, [[cephalosporin]]s, [[beta-lactam]]-[[Β-Lactamase inhibitor|betalactamase inhibitor]] combinations (such as [[Piperacillin/tazobactam|piperacillin-tazobactam]]), [[Antifolate|folate antagonist]]s, [[quinolone antibiotic|quinolones]], and [[carbapenem]]s. Many of these antibiotics also cover Gram-positive bacteria. The antibiotics that specifically target Gram-negative organisms include [[aminoglycoside]]s, [[monobactam]]s (such as [[aztreonam]]), and [[ciprofloxacin]]. | ||
== Characteristics == | == Characteristics == | ||
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[[File:Gram-Cell-wall.svg|thumb|right|[[Gram-positive]] and -negative [[bacteria]] are differentiated chiefly by their [[cell wall]] structure]] | [[File:Gram-Cell-wall.svg|thumb|right|[[Gram-positive]] and -negative [[bacteria]] are differentiated chiefly by their [[cell wall]] structure]] | ||
Conventional | Conventional Gram-negative (LPS-diderm) bacteria display {{nowrap|the following characteristics}}:{{cn|date=July 2022}} | ||
* An inner [[cell membrane]] is present ([[cytoplasm]]ic) | * An inner [[cell membrane]] is present ([[cytoplasm]]ic) | ||
* A thin [[peptidoglycan]] layer is present (this is much thicker in | * A thin [[peptidoglycan]] layer is present (this is much thicker in Gram-positive bacteria) | ||
* Has [[Bacterial outer membrane|outer membrane]] containing [[lipopolysaccharide]]s (LPS, which consists of [[lipid A]], core [[polysaccharide]], and [[O antigen]]) in its outer leaflet and [[phospholipid]]s in the inner leaflet | * Has [[Bacterial outer membrane|outer membrane]] containing [[lipopolysaccharide]]s (LPS, which consists of [[lipid A]], core [[polysaccharide]], and [[O antigen]]) in its outer leaflet and [[phospholipid]]s in the inner leaflet | ||
* [[Porin (protein)|Porins]] exist in the outer membrane, which act like pores for particular molecules | * [[Porin (protein)|Porins]] exist in the outer membrane, which act like pores for particular molecules | ||
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However, the LPS-diderm group (corresponding to kingdom [[Pseudomonadati]], formerly "Hydrobacteria") is not the only type of bacteria that stain negative.<ref name="valid-dom-kingdom">{{cite journal |last1=Göker |first1=Markus |last2=Oren |first2=Aharon |title=Valid publication of names of two domains and seven kingdoms of prokaryotes |journal=International Journal of Systematic and Evolutionary Microbiology |date=22 January 2024 |volume=74 |issue=1 |doi=10.1099/ijsem.0.006242|pmid=38252124 |doi-access=free }}</ref> ''[[Mycobacterium]]'' (or rather most of [[Mycobacteriales]]), which does not belong in the group, have independently evolved an outer cell membrane, with a cell wall made of [[mycolic acid]].<ref name=Gupta19myc>{{cite journal |last1=Gupta |first1=Radhey S. |title=Commentary: Genome-Based Taxonomic Classification of the Phylum Actinobacteria |journal=Frontiers in Microbiology |date=22 February 2019 |volume=10 |page=206 |doi=10.3389/fmicb.2019.00206 |quote=Mycolic acids are important constituents of the cell envelopes of most members.|doi-access=free |pmid=30853945 |pmc=6395429 }}</ref> This gives it very different structure and features.<ref name="Desvaux et al., 2009"/><ref name="Sutcliffe, 2010"/><ref name="Guptac"/><ref name="pmid19667386">{{cite journal|vauthors=Marchandin H, Teyssier C, Campos J, Jean-Pierre H, Roger F, Gay B, Carlier JP, Jumas-Bilak E |title=Negativicoccus succinicivorans gen. nov., sp. nov., isolated from human clinical samples, emended description of the family Veillonellaceae and description of Negativicutes classis nov., Selenomonadales ord. nov. and Acidaminococcaceae fam. nov. in the bacterial phylum Firmicutes |journal=Int. J. Syst. Evol. Microbiol. |volume=60 |issue=Pt 6 |pages=1271–9 |date=June 2010 |pmid=19667386 |doi=10.1099/ijs.0.013102-0|doi-access=free }}</ref> | However, the LPS-diderm group (corresponding to kingdom [[Pseudomonadati]], formerly "Hydrobacteria") is not the only type of bacteria that stain negative.<ref name="valid-dom-kingdom">{{cite journal |last1=Göker |first1=Markus |last2=Oren |first2=Aharon |title=Valid publication of names of two domains and seven kingdoms of prokaryotes |journal=International Journal of Systematic and Evolutionary Microbiology |date=22 January 2024 |volume=74 |issue=1 |doi=10.1099/ijsem.0.006242|pmid=38252124 |doi-access=free }}</ref> ''[[Mycobacterium]]'' (or rather most of [[Mycobacteriales]]), which does not belong in the group, have independently evolved an outer cell membrane, with a cell wall made of [[mycolic acid]].<ref name=Gupta19myc>{{cite journal |last1=Gupta |first1=Radhey S. |title=Commentary: Genome-Based Taxonomic Classification of the Phylum Actinobacteria |journal=Frontiers in Microbiology |date=22 February 2019 |volume=10 |page=206 |doi=10.3389/fmicb.2019.00206 |quote=Mycolic acids are important constituents of the cell envelopes of most members.|doi-access=free |pmid=30853945 |pmc=6395429 }}</ref> This gives it very different structure and features.<ref name="Desvaux et al., 2009"/><ref name="Sutcliffe, 2010"/><ref name="Guptac"/><ref name="pmid19667386">{{cite journal|vauthors=Marchandin H, Teyssier C, Campos J, Jean-Pierre H, Roger F, Gay B, Carlier JP, Jumas-Bilak E |title=Negativicoccus succinicivorans gen. nov., sp. nov., isolated from human clinical samples, emended description of the family Veillonellaceae and description of Negativicutes classis nov., Selenomonadales ord. nov. and Acidaminococcaceae fam. nov. in the bacterial phylum Firmicutes |journal=Int. J. Syst. Evol. Microbiol. |volume=60 |issue=Pt 6 |pages=1271–9 |date=June 2010 |pmid=19667386 |doi=10.1099/ijs.0.013102-0|doi-access=free }}</ref> | ||
In many | In many Gram-negative bacteria, the [[IgaA]] membrane protein negatively regulates the Rcs phosphorelay system, a key envelope stress response pathway that helps maintain cell envelope integrity. | ||
== Classification == | == Classification == | ||
Along with cell shape, [[Gram stain]]ing is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria. | Along with cell shape, [[Gram stain]]ing is a rapid diagnostic tool and once was used to group species at the subdivision of Bacteria. | ||
[[Bacterial taxonomy#History|Historically]], the kingdom [[Monera]] was divided into four [[Taxonomic rank|divisions]] based on Gram staining: [[Bacillota|Firmicutes]] (+), [[Gracilicutes|Gracillicutes]] (−), [[Mollicutes]] (0) and [[Methanogen|Mendocutes]] (var.).<ref>{{cite journal |last1=Gibbons |first1=N. E. |last2=Murray |first2=R. G. E. |title=Proposals Concerning the Higher Taxa of Bacteria |journal=International Journal of Systematic Bacteriology |year=1978 |volume=28 |issue=1 |pages=1–6 |doi=10.1099/00207713-28-1-1 |doi-access=free }}</ref> | [[Bacterial taxonomy#History|Historically]], the kingdom [[Monera]] was divided into four [[Taxonomic rank|divisions]] based on Gram staining: [[Bacillota|Firmicutes]] (+), [[Gracilicutes|Gracillicutes]] (−), [[Mollicutes]] (0) and [[Methanogen|Mendocutes]] (var.).<ref>{{cite journal |last1=Gibbons |first1=N. E. |last2=Murray |first2=R. G. E. |title=Proposals Concerning the Higher Taxa of Bacteria |journal=International Journal of Systematic Bacteriology |year=1978 |volume=28 |issue=1 |pages=1–6 |doi=10.1099/00207713-28-1-1 |doi-access=free }}</ref> | ||
Since 1987, the [[monophyly]] of the | Since 1987, the [[monophyly]] of the Gram-negative bacteria has been [[Proof (truth)|disproven]] with [[Molecular phylogenetics|molecular studies]].<ref name="woese87">{{cite journal | author = Woese CR | title = Bacterial evolution | journal = Microbiol. Rev. | volume = 51 | issue = 2 | pages = 221–71 |date=June 1987 | pmid = 2439888 | pmc = 373105 | doi = 10.1128/MMBR.51.2.221-271.1987}}</ref> | ||
Current knowledge divides the | 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 kingdom [[Pseudomonadati]].<ref name="valid-dom-kingdom"/> The less conventional ones are, as mentioned above, the order [[Mycobacteriales]], have a [[mycolic acid]] cell wall and an outer membrane.<ref name=Gupta19myc/> 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. | ||
== Taxonomy == | == Taxonomy == | ||
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{{Technical|section|date=March 2014}} | {{Technical|section|date=March 2014}} | ||
{{Split section|Gram stain|discuss=Gram stain#Move Taxonomy sections here |date=November 2023}} | {{Split section|Gram stain|discuss=Gram stain#Move Taxonomy sections here |date=November 2023}} | ||
Bacteria are traditionally classified based on their [[Gram stain|Gram-staining]] response into the [[ | Bacteria are traditionally classified based on their [[Gram stain|Gram-staining]] response into the [[Gram-positive]] and Gram-negative bacteria. Having just one membrane, 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 the staining result.<ref name="Guptab">{{cite journal|last=Gupta |first=RS |title=Protein phylogenies and signature sequences: A reappraisal of evolutionary relationships among archaebacteria, eubacteria, and eukaryotes |journal=Microbiol. Mol. Biol. Rev. |volume=62 |issue=4 |pages=1435–91 |date=December 1998 |pmid=9841678 |pmc=98952 |doi=10.1128/MMBR.62.4.1435-1491.1998}}</ref><ref name="Guptad">{{cite journal | author = Gupta RS | title = The natural evolutionary relationships among prokaryotes | journal = Crit. Rev. Microbiol. | volume = 26 | issue = 2 | pages = 111–31 | year = 2000 | pmid = 10890353 | doi = 10.1080/10408410091154219 | url = http://www.life.illinois.edu/govindjee/Part2/15_Gupta.pdf | citeseerx = 10.1.1.496.1356 | s2cid = 30541897 | access-date = 2017-10-24 | archive-date = 2018-07-20 | archive-url = https://web.archive.org/web/20180720153253/http://www.life.illinois.edu/govindjee/Part2/15_Gupta.pdf | url-status = live }}</ref><ref name="Desvaux et al., 2009">{{cite journal |vauthors=Desvaux M, Hébraud M, Talon R, Henderson IR | title = Secretion and subcellular localizations of bacterial proteins: a semantic awareness issue | journal = Trends Microbiol. | volume = 17 | issue = 4 | pages = 139–45 |date=April 2009 | pmid = 19299134 | doi = 10.1016/j.tim.2009.01.004 }}</ref><ref name="Sutcliffe, 2010">{{cite journal | author = Sutcliffe IC | title = A phylum level perspective on bacterial cell envelope architecture | journal = Trends Microbiol. | volume = 18 | issue = 10 | pages = 464–70 |date=October 2010 | pmid = 20637628 | doi = 10.1016/j.tim.2010.06.005 }}</ref> 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 [[bacterial outer membrane|outer lipid membrane]].<ref name="Guptab"/><ref name="Guptaa">{{cite journal | author = Gupta RS | title = What are archaebacteria: life's third domain or monoderm prokaryotes related to gram-positive bacteria? A new proposal for the classification of prokaryotic organisms | journal = Mol. Microbiol. | volume = 29 | issue = 3 | pages = 695–707 |date=August 1998 | pmid = 9723910 | doi = 10.1046/j.1365-2958.1998.00978.x | doi-access = free }}</ref> | ||
Of these two structurally distinct groups of [[Prokaryote|prokaryotic]] organisms, monoderm prokaryotes are thought to be ancestral. Based upon a number of different observations, including that the | Of these two structurally distinct groups of [[Prokaryote|prokaryotic]] 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 to [[antibiotics]] and that the Gram-negative bacteria are, in general, [[antimicrobial resistance|resistant]] to antibiotics, it has been proposed that the outer cell membrane in Gram-negative bacteria (diderms) evolved as a protective mechanism against antibiotic [[Evolutionary pressure|selection pressure]].<ref name="Guptab"/><ref name="Guptad"/><ref name="Guptaa"/><ref name="Guptac">{{cite journal | author = Gupta RS | title = Origin of diderm (gram-negative) bacteria: antibiotic selection pressure rather than endosymbiosis likely led to the evolution of bacterial cells with two membranes | journal = Antonie van Leeuwenhoek | volume = 100 | issue = 2 | pages = 171–82 |date=August 2011 | pmid = 21717204 | pmc = 3133647 | doi = 10.1007/s10482-011-9616-8 }}</ref> Some bacteria such as ''[[Deinococcus]]'', which stain Gram-positive due to 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.<ref name="Guptab"/><ref name="Guptac"/> | ||
The conventional LPS-''diderm'' group of | 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 few [[conserved signature indel]] (CSI) in the [[HSP60]] ([[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 a [[Monophyly|monophyletic]] [[clade]] and that no loss of the outer membrane from any species from this group has occurred.<ref name="Guptac"/> They have accordingly been assigned a kingdom [[Pseudomonadati]] (formerly "Hydrobacteria").<ref name="valid-dom-kingdom"/> | ||
The difficulty lies in the other taxa that also have a diderm structure. | The difficulty lies in the other taxa that also have a diderm structure. | ||
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=== Example species === | === Example species === | ||
The [[proteobacteria]] are a major superphylum of | The [[proteobacteria]] are a major superphylum of Gram-negative bacteria, including ''[[Escherichia coli|E. coli]]'', ''[[Salmonella]]'', ''[[Shigella]]'', and other [[Enterobacteriaceae]], ''[[Pseudomonas]]'', ''[[Moraxella catarrhalis|Moraxella]]'', ''[[Helicobacter]]'', ''[[Stenotrophomonas]]'', ''[[Bdellovibrio]]'', [[acetic acid bacteria]], ''[[Legionella]]'' etc. Other notable groups of Gram-negative bacteria include the [[cyanobacteria]], [[spirochaete]]s, and [[green sulfur bacteria]].<ref>{{Citation |last=Castenholz |first=Richard W. |title=General Characteristics of the Cyanobacteria |date=2015 |work=Bergey's Manual of Systematics of Archaea and Bacteria |pages=1–23 |url=https://onlinelibrary.wiley.com/doi/10.1002/9781118960608.cbm00019 |access-date=2025-01-25 |publisher=John Wiley & Sons, Ltd |language=en |doi=10.1002/9781118960608.cbm00019 |isbn=978-1-118-96060-8|url-access=subscription }}</ref><ref>{{Citation |last=Cole |first=John R. |title=5 - Spirochetes |date=1990-01-01 |work=Diagnostic Procedure in Veterinary Bacteriology and Mycology (Fifth Edition) |pages=41–60 |editor-last=Carter |editor-first=G. R. |url=https://linkinghub.elsevier.com/retrieve/pii/B9780121617752500098 |access-date=2025-01-25 |place=San Diego |publisher=Academic Press |doi=10.1016/b978-0-12-161775-2.50009-8 |isbn=978-0-12-161775-2 |editor2-last=Cole |editor2-first=John R.|url-access=subscription }}</ref><ref>{{Cite book |last=Schmidt |first=Thomas M. |title=Encyclopedia of Microbiology |date=2019 |publisher=Elsevier Science & Technology |isbn=978-0-12-811737-8 |edition=4th |location=San Diego |pages=527–537}}</ref> | ||
Medically-relevant | Medically-relevant Gram-negative [[diplococci]] include the four types that cause a [[sexually transmitted disease]] (''[[Neisseria gonorrhoeae]]''<ref name=Yeshanew_2018>{{cite journal |last1=Yeshanew |first1=Addisu Gize |last2=Geremew |first2=Rozina Ambachew |date=2018-07-17 |title=MNeisseria Gonorrhoae and their antimicrobial susceptibility patterns among symptomatic patients from Gondar town, north West Ethiopia |journal=Antimicrobial Resistance and Infection Control |volume=7 |issue=85 |page=85 |doi=10.1186/s13756-018-0376-3 |doi-access=free |pmid=30026943 |pmc=6050735 }}</ref>), a [[meningitis]] (''[[Neisseria meningitidis]]''<ref name="CDC 2018 y478">{{cite web | title=Vaccine Preventable Diseases Surveillance Manual | website=CDC | date=April 3, 2018 | url=https://www.cdc.gov/vaccines/pubs/surv-manual/chpt08-mening.html | access-date=January 26, 2024}}</ref>), and respiratory symptoms (''[[Moraxella catarrhalis]]'',<ref name=Verduin_2002>{{cite journal |last1=Verduin |first1=Cees M. |last2=Hol |first2=Cees |last3=Fleer |first3=Andre |last4=van Dijk |first4=Hans |last5=van Belkum |first5=Alex |date=January 2002 |title=Moraxella catarrhalis: from Emerging to Established Pathogen |journal=Clinical Microbiology Reviews |volume=15 |issue=1 |pages=125–144 |doi=10.1128/CMR.15.1.125-144.2002 |pmid=11781271 |pmc=118065 }}</ref> A [[coccobacillus]] ''[[Haemophilus influenzae]]'' is another medically relevant coccal type.<ref name="CDC 2018 b143">{{cite web | title=For Clinicians: Haemophilus influenzae | website=CDC | date=February 13, 2018 | url=https://www.cdc.gov/hi-disease/clinicians.html#:~:text=Haemophilus%20influenzae%20is%20a%20pleomorphic,that%20have%20distinct%20capsular%20polysaccharides. | access-date=January 26, 2024}}</ref> | ||
Medically relevant | Medically relevant Gram-negative [[bacillus (shape)|bacilli]] 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]]'').{{cn|date=November 2023}} | ||
Gram-negative bacteria associated with [[hospital-acquired infection]]s include ''[[Acinetobacter baumannii]]'', which cause [[bacteremia]], secondary [[meningitis]], and [[ventilator-associated pneumonia]] in hospital [[intensive-care unit]]s. | Gram-negative bacteria associated with [[hospital-acquired infection]]s include ''[[Acinetobacter baumannii]]'', which cause [[bacteremia]], secondary [[meningitis]], and [[ventilator-associated pneumonia]] in hospital [[intensive-care unit]]s. | ||
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[[Transformation (genetics)|Transformation]] is one of three processes for [[horizontal gene transfer]], in which exogenous genetic material passes from one [[Bacteria|bacterium]] to another, the other two being [[bacterial conjugation|conjugation]] (transfer of [[plasmid|genetic material]] between two bacterial cells in direct contact) and [[transduction (genetics)|transduction]] (injection of foreign DNA by a [[bacteriophage]] virus into the host bacterium).<ref name=Johnston>{{cite journal |vauthors=Johnston C, Martin B, Fichant G, Polard P, Claverys JP |title=Bacterial transformation: distribution, shared mechanisms and divergent control |journal=Nat. Rev. Microbiol. |volume=12 |issue=3 |pages=181–96 |year=2014 |pmid=24509783 |doi=10.1038/nrmicro3199 |s2cid=23559881 }}</ref><ref name=Korotetskiy>{{cite journal |vauthors=Korotetskiy I, Shilov S, Kuznetsova T, Kerimzhanova B, Korotetskaya N, Ivanova L, Zubenko N, Parenova R, Reva O |title=Analysis of Whole-Genome Sequences of Pathogenic Gram-Positive and Gram-Negative Isolates from the Same Hospital Environment to Investigate Common Evolutionary Trends Associated with Horizontal Gene Exchange, Mutations and DNA Methylation Patterning |journal=Microorganisms |volume=11 |issue=2 |year=2023 |page=323 |pmid=36838287 |doi=10.3390/microorganisms11020323 |doi-access=free |pmc=9961978 }}</ref> In transformation, the [[Nucleic acid|genetic material]] passes through the intervening medium, and uptake is completely dependent on the recipient bacterium.<ref name=Johnston/> | [[Transformation (genetics)|Transformation]] is one of three processes for [[horizontal gene transfer]], in which exogenous genetic material passes from one [[Bacteria|bacterium]] to another, the other two being [[bacterial conjugation|conjugation]] (transfer of [[plasmid|genetic material]] between two bacterial cells in direct contact) and [[transduction (genetics)|transduction]] (injection of foreign DNA by a [[bacteriophage]] virus into the host bacterium).<ref name=Johnston>{{cite journal |vauthors=Johnston C, Martin B, Fichant G, Polard P, Claverys JP |title=Bacterial transformation: distribution, shared mechanisms and divergent control |journal=Nat. Rev. Microbiol. |volume=12 |issue=3 |pages=181–96 |year=2014 |pmid=24509783 |doi=10.1038/nrmicro3199 |s2cid=23559881 }}</ref><ref name=Korotetskiy>{{cite journal |vauthors=Korotetskiy I, Shilov S, Kuznetsova T, Kerimzhanova B, Korotetskaya N, Ivanova L, Zubenko N, Parenova R, Reva O |title=Analysis of Whole-Genome Sequences of Pathogenic Gram-Positive and Gram-Negative Isolates from the Same Hospital Environment to Investigate Common Evolutionary Trends Associated with Horizontal Gene Exchange, Mutations and DNA Methylation Patterning |journal=Microorganisms |volume=11 |issue=2 |year=2023 |page=323 |pmid=36838287 |doi=10.3390/microorganisms11020323 |doi-access=free |pmc=9961978 }}</ref> In transformation, the [[Nucleic acid|genetic material]] passes through the intervening medium, and uptake is completely dependent on the recipient bacterium.<ref name=Johnston/> | ||
As of 2014 about 80 species of bacteria were known to be capable of transformation, about evenly divided between [[ | 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.<ref name=Johnston/> 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]]''.<ref name=Seitz>{{cite journal |vauthors=Seitz P, Blokesch M |title=Cues and regulatory pathways involved in natural competence and transformation in pathogenic and environmental Gram-negative bacteria |journal=FEMS Microbiol. Rev. |volume=37 |issue=3 |pages=336–63 |year=2013 |pmid=22928673 |doi=10.1111/j.1574-6976.2012.00353.x |doi-access=free }}</ref> 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]]''.<ref name=Seitz/> | ||
==Role in disease== | ==Role in disease== | ||
[[File:Diagnostic algorithm of possible bacterial infection.png|thumb|Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Clinically significant | [[File:Diagnostic algorithm of possible bacterial infection.png|thumb|Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Clinically significant Gram-negative bacteria are usually rods, as shown near bottom right. Although some Gram-negative bacteria can be recognized by "bench tests", diagnosis in the modern microbiology lab usually involves [[MALDI-TOF]] and/or multitarget assay.]] | ||
One of the several unique characteristics of | One of 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 [[Lipopolysaccharide|endotoxin]].<ref name=Baron/> If Gram-negative bacteria enter the [[circulatory system]], LPS can trigger an [[innate immune response]], activating the [[immune system]] and producing [[cytokine]]s (hormonal regulators). This leads to [[inflammation]] and can cause a toxic reaction, resulting in fever, an increased respiratory rate, and [[Hypotension|low blood pressure]]. That is why some infections with Gram-negative bacteria can lead to life-threatening [[septic shock]].<ref name="ww.ncbi.nlm.nih.gov"/> | ||
The outer membrane protects the bacteria from several [[antibiotic]]s, [[dye]]s, and [[detergent]]s 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 [[Periplasm|periplasmic space]] (space between the two cell membranes) also contains [[enzyme]]s which break down or modify antibiotics. Drugs commonly used to treat | The outer membrane protects the bacteria from several [[antibiotic]]s, [[dye]]s, and [[detergent]]s 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 [[Periplasm|periplasmic space]] (space between the two cell membranes) also contains [[enzyme]]s which break down or modify antibiotics. Drugs commonly used to treat Gram negative infections include amino, carboxy and ureido penicillins ([[ampicillin]], [[amoxicillin]], [[Piperacillin|pipercillin]], [[ticarcillin]]). These drugs may be combined with [[beta-lactamase inhibitor]]s to combat the presence of enzymes that can digest these drugs (known as [[beta-lactamase]]s) in the peri-plasmic space. Other classes of drugs that have Gram negative spectrum include [[cephalosporin]]s, [[monobactam]]s ([[aztreonam]]), [[Aminoglycoside|aminoglycosides]], [[quinolone antibiotic|quinolones]], [[macrolide]]s, [[chloramphenicol]], [[Antifolate|folate antagonists]], and [[carbapenem]]s.<ref>{{cite web|last=Glück|first=Thomas|url=https://www.jwatch.org/id200312120000007/2003/12/12/gram-negative-bacteria-and-broad-spectrum|title=Gram-Negative Bacteria and Broad-Spectrum Antibiotics: Good News Except for Fluoroquinolones|publisher=NEJM Journal Watch|website=www.jwatch.org|date=12 December 2003|access-date=10 March 2018|archive-date=10 March 2018|archive-url=https://web.archive.org/web/20180310074653/https://www.jwatch.org/id200312120000007/2003/12/12/gram-negative-bacteria-and-broad-spectrum|url-status=live}}</ref> | ||
== Orthography: capitalization == | == Orthography: capitalization == | ||
<!--Please keep this text synched with that of [[Gram-positive bacteria#Orthographic note]].--> | <!--Please keep this text synched with that of [[Gram-positive bacteria#Orthographic note]].--> | ||
The adjectives '' | The adjectives ''Gram-positive'' and ''Gram-negative'' derive from the surname of [[Hans Christian Gram]], a Danish bacteriologist; as [[Eponym#Orthographic conventions|eponymous adjectives]], their initial letter ''G'' can be either capital or lower-case, depending on which [[style guide]] (e.g., that of the [[Centers for Disease Control and Prevention|CDC]]), if any, governs the document being written.<ref>{{cite web |publisher=Centers for Disease Control and Prevention |title=Preferred Usage - Emerging Infectious Disease journal - CDC |url=https://wwwnc.cdc.gov/eid/page/preferred-usage |work=CDC.gov |access-date=2018-03-04 |archive-date=2018-01-29 |archive-url=https://web.archive.org/web/20180129223909/https://wwwnc.cdc.gov/eid/page/preferred-usage |url-status=live }}</ref> This is further explained at ''[[Gram staining#Orthographic note|Gram staining § Orthographic note]]''. | ||
== See also == | == See also == | ||
* [[Autochaperone]] | * [[Autochaperone]] | ||
* [[Gram stain#Gram-variable and gram-indeterminate bacteria|Gram-variable and | * [[Gram stain#Gram-variable and gram-indeterminate bacteria|Gram-variable and Gram-indeterminate bacteria]] | ||
* [[OMPdb]] (2011) | * [[OMPdb]] (2011) | ||
* [[Outer membrane receptor]] | * [[Outer membrane receptor]] | ||
| Line 90: | Line 90: | ||
== External links == | == External links == | ||
* [https://web.archive.org/web/20081222045655/http://opm.phar.umich.edu:80/localization.php?localization=Bacterial%20gram-negative%20inner%20membrane 3D structures of proteins from inner membranes of Ellie Wyithe's | * [https://web.archive.org/web/20081222045655/http://opm.phar.umich.edu:80/localization.php?localization=Bacterial%20gram-negative%20inner%20membrane 3D structures of proteins from inner membranes of Ellie Wyithe's Gram-negative bacteria] | ||
{{Bacteria}} | {{Bacteria}} | ||
Latest revision as of 14:04, 23 September 2025
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.[1] Their defining characteristic is that their cell envelope consists of a thin peptidoglycan cell wall sandwiched between an inner (cytoplasmic) membrane and an outer membrane.[2] These bacteria are found in all environments that support life on Earth.
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 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.[3]
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.
Characteristics
Conventional Gram-negative (LPS-diderm) bacteria display the following characteristics:Script error: No such module "Unsubst".
- An inner cell membrane is present (cytoplasmic)
- A thin peptidoglycan layer is present (this is much thicker in Gram-positive bacteria)
- Has outer membrane containing lipopolysaccharides (LPS, which consists of lipid A, core polysaccharide, and O antigen) in its outer leaflet and phospholipids in the inner leaflet
- Porins exist in the outer membrane, which act like pores for particular molecules
- Between the outer membrane and the cytoplasmic membrane there is a space filled with a concentrated gel-like substance called periplasm
- The S-layer is directly attached to the outer membrane rather than to the peptidoglycan
- If present, flagella have four supporting rings instead of two
- Teichoic acids or lipoteichoic acids are absent
- Lipoproteins are attached to the polysaccharide backbone
- Some contain Braun's lipoprotein, which serves as a link between the outer membrane and the peptidoglycan chain by a covalent bond
- Most, with few exceptions, do not form spores
However, the LPS-diderm group (corresponding to kingdom Pseudomonadati, formerly "Hydrobacteria") is not the only type of bacteria that stain negative.[4] Mycobacterium (or rather most of Mycobacteriales), which does not belong in the group, have independently evolved an outer cell membrane, with a cell wall made of mycolic acid.[5] This gives it very different structure and features.[6][7][8][9]
In many Gram-negative bacteria, the IgaA membrane protein negatively regulates the Rcs phosphorelay system, a key envelope stress response pathway that helps maintain cell envelope integrity.
Classification
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: Firmicutes (+), Gracillicutes (−), Mollicutes (0) and Mendocutes (var.).[10] Since 1987, the monophyly of the Gram-negative bacteria has been disproven with molecular studies.[11]
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 kingdom Pseudomonadati.[4] The less conventional ones are, as mentioned above, the order Mycobacteriales, have a mycolic 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.
Taxonomy
Script error: No such module "Labelled list hatnote". Script error: No such module "labelled list hatnote". Script error: No such module "Unsubst". Script error: No such module "Unsubst". Bacteria are traditionally classified based on their Gram-staining response into the Gram-positive and Gram-negative bacteria. Having just one membrane, 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 the staining result.[12][13][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 an outer lipid membrane.[12][14]
Of these two structurally distinct groups of prokaryotic 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 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.[12][13][14][8] Some bacteria such as Deinococcus, which stain Gram-positive due to 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.[12][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 few conserved signature indel (CSI) in the HSP60 (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 a monophyletic clade and that no loss of the outer membrane from any species from this group has occurred.[8] They have accordingly been assigned a kingdom Pseudomonadati (formerly "Hydrobacteria").[4]
The difficulty lies in the other taxa that also have a diderm structure.
- The first group is paraphyletic. It includes a number of taxa (including Negativicutes, Fusobacteriota, Synergistota, and Elusimicrobiota) that are either part of the phylum Bacillota (a monoderm group) or branches in its proximity.[7][8][9] They lack the GroEL CSI signature, which is proof that they do not belong in the former group.[8] Some members are likely monoderm, just with a very thin layer of LPS to not appear on the stain. Others have more convoluted structures.[15]
- The second group are the clinically-relevant Mycobacterium, expanding to most of its encompassing order of Mycobacteriales. They do not have the CSI, and their cell wall is made of a different substance: mycolic acid.[5]
Example species
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 the cyanobacteria, spirochaetes, and green sulfur bacteria.[16][17][18]
Medically-relevant Gram-negative diplococci include the four types that cause a sexually transmitted disease (Neisseria gonorrhoeae[19]), a meningitis (Neisseria meningitidis[20]), and respiratory symptoms (Moraxella catarrhalis,[21] A coccobacillus Haemophilus influenzae is another medically relevant coccal type.[22]
Medically relevant Gram-negative bacilli 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).Script error: No such module "Unsubst".
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.
Bacterial transformation
Transformation 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).[23][24] In transformation, the genetic material passes through the intervening medium, and uptake is completely dependent on the recipient bacterium.[23]
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.[23] 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.[25] 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.[25]
Role in disease
One of 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.[1] 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 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.[3]
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 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 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.[26]
Orthography: capitalization
The adjectives Gram-positive and Gram-negative derive from the surname of Hans Christian Gram, a Danish bacteriologist; as eponymous adjectives, their initial letter G can be either capital or lower-case, depending on which style guide (e.g., that of the CDC), if any, governs the document being written.[27] This is further explained at Gram staining § Orthographic note.
See also
References
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Notes
External links
Template:Bacteria Template:Bacteria classification Template:Portal bar Template:Authority control
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