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| {{About0|Mycoplasma pneumonia}} | | {{About0|Mycoplasma pneumonia}} |
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| Etiologic Agent: Mycoplasma pneumonia is a type of atypical pneumonia. It is caused by the bacteria M. pneumoniae. This type of pneumonia usually affects people younger than 40. Various studies suggest that it makes up 15 - 50% of all pneumonia cases in adults and even more in school-aged children.
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| People at highest risk for mycoplasma pneumonia include those living or working in crowded areas such as schools and homeless shelters, although many people who contract mycoplasma pneumonia have no identifiable risk factor.
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| Mycoplasma pneumoniae, a small bacterium. This class of organisms lack a peptidoglycan cell wall present on all other firmicute bacteria. Instead, it has a cell membrane which incorporates sterol compounds, similar to eukaryotic cells. It obtains these sterols from the host serum, allowing it to retain a simple structure. Lacking a cell wall, these organisms are resistant to the effects of penicillins and other beta-lactam antibiotics, which act by disrupting the bacterial cell wall.
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| M. pneumoniae has one of the smallest genomes known, with 816 kilobase pairs (kbs). Its genome and proteome has been fully characterized. It uses some unique genetic code, making its code more similar to mitochondria than to other bacteria. Thus it is said that Mycoplasma pneumoniae has a degenerate genome. It lacks the cellular machinery for making many essential compounds, including new purines and pyrimidines. It also has no tri-carboxylic acid cycle and an incomplete electron transport chain. Because of this, it is an obligate parasite.
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| ==Overview== | | ==Overview== |
| '''''Mycoplasma pneumoniae''''' is a very small [[bacterium]] in the class [[Mollicutes]]. | | ''Mycoplasma'' pneumonia is caused by ''Mycoplasma pneumoniae'', a small bacterial agent that lacks cell wall and periplasmic space. On Gram-stain, '''Mycoplasma'' stains pink, i.e. it is Gram-negative by staining. However, it is structurally different from other Gram-negative organisms because it lacks a cell wall. |
| It is a human pathogen that causes the disease [[mycoplasma pneumonia]], a form of [[Atypical pneumonia|atypical]] [[bacterial pneumonia|bacterial]] [[pneumonia]] related to [[cold agglutinin disease]]. ''M. pneumoniae'' is characterized by the absence of a [[peptidoglycan cell wall]] and resulting resistance to many [[Antibacterial|antibacterial agents]]. The persistence of ''M. pneumoniae'' infections even after treatment is associated with its ability to mimic [[host cell]] surface composition.
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| ==Discovery and history==
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| In 1898, Nocard and Roux were the first to isolate a [[mycoplasma]] species in culture from [[Bovinae|bovine]], however it wasn't until 1944 when ''Mycoplasma pneumoniae'', known then as Eaton agent or Eaton's agent,<ref>{{cite journal |author=A.S. Dajani, W.A. Clyde Jr. and F.W. Denny |year=1965 |title=Experimental Infection with ''Mycoplasma Pneumoniae'' (Eaton's Aagent) |journal=The Journal of Experimental Medicine |volume=121 |issue= 6|pages=1071–1086 |pmid=14319403 |url= |accessdate= |quote= |doi=10.1084/jem.121.6.1071 |pmc=2138014 }}</ref> was isolated and described from a patient with [[primary atypical pneumonia]].<ref name=Waites/>
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| Initially ''M. pneumoniae'' was considered as a [[virus]] rather than a bacterium, when Eaton and colleagues cultured the causative agent of human [[primary atypical pneumonia]] (PAP) or "[[walking pneumonia]]".<ref name=Eaton>{{cite journal |author=Eaton MD, Meiklejohn G, van Herrick W, Corey M |title=STUDIES ON THE ETIOLOGY OF PRIMARY ATYPICAL PNEUMONIA : III. SPECIFIC NEUTRALIZATION OF THE VIRUS BY HUMAN SERUM |journal=J. Exp. Med. |volume=82 |issue= 5|pages=329–42 |year=1945 |pmid= 19871504|pmc= 2135563|doi= 10.1084/jem.82.5.329|url=}}</ref> The terms '[[walking pneumonia]]' and 'atypical pneumonia' were coined to describe the unresponsiveness of [[pneumonia]] inducing ''M. pneumoniae'' infections to [[antibiotics]] like [[penicillin]].<ref name=Waites/> Eaton's agent could be grown in chicken [[embryos]] and passed through a filter that excluded normal bacteria. Eaton suggested the possibility that the disease was caused by a mycoplasma, but the agent did not grow on the standard [[pleuropneumonia-like organism]] (PPLO) media of the time. These observations led to the conclusion that the causative agent of PAP was a virus. Researchers at that time showed that the cultured agent could induce disease in experimentally infected cotton rats and hamsters. In spite of controversy whether the researchers had truly isolated the causative agent of PAP (based largely on the unusual immunological response of patients with PAP), in retrospect their evidence along with that of colleagues and competitors appears to have been quite conclusive.<ref name=Marmion_1990>{{cite journal |author=B.P. Marmion|title=Eaton agent—science and scientific acceptance: a historical commentary |journal=Rev. Infect. Dis. |volume=12 |issue=2 |pages=338–53 |year=1990 |pmid=2109871 |doi= 10.1093/clinids/12.2.338|url=}}</ref> There were reports linking Eaton agent to the PPLOs or mycoplasmas, well known then as parasites of cattle and rodents, due to sensitivity to antimicrobials. Studies that followed until 1963 determined that Eaton’s agent was a [[bacterium]] that caused human [[lower respiratory tract infection]]s.<ref name=Waites/>
| | ==Clinical Significance== |
| | ''M. pneumoniae'' is the causative agent responsible for ''Mycoplasma'' pneumonia, an atypical pneumonia common in children and young adults. |
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| ==Taxonomy and classification== | | ==Taxonomy== |
| | | *Bacteria; Firmicutes; Mollicutes; Mycoplasmatales; Mycoplasmataceae; ''Mycoplasma pneumoniae'' |
| The term [[mycoplasma]] (“mykes”, meaning fungus and “plasma”, meaning formed) is derived from the [[fungal]]-like growth of some mycoplasma species.<ref name=Waites/> The mycoplasmas were classified as [[Mollicutes]] (“mollis”, meaning soft and “cutis”, meaning skin) in 1960 due to their small size and [[genome]], lack of [[cell wall]], low [[G-C content|G+C content]] and unusual [[nutritional]] needs.<ref name=Waites/><ref name=Weisburg>{{cite journal | last1 = Weisburg | first1 = W. G. | last2 = Tully | first2 = J. G. | last3 = Rose | first3 = D. L. | last4 = Pretzel | first4 = J.P. | last5 = Oyaizu | first5 = H. | last6 = Yang | first6 = D. | last7 = Mandelco | first7 = L. | last8 = Sechrest | first8 = J. | last9 = Lawrence | first9 = T. G. | last10 = Etten | first10 = J. Van | year = 1989 | title = A phylogenetic analysis of the mycoplasmas: basis for their classification | url = | journal = J. Bacteriol | volume = 171 | issue = | pages = 6455–6467 }}</ref> ''M. pneumoniae'' has also been designated as an [[arginine]] non[[Fermentation|ferment]]ing species.<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> Mycoplasmas are further [[Taxonomic classification|classified]] by the sequence composition of [[16S ribosomal RNA|16s rRNA]]. All mycoplasmas of the ''pneumoniae'' group possess similar 16s rRNA variations unique to the group, of which ''M. pneumoniae'' has a 6.3% variation in the [[conservation (genetics)|conserved regions]], that suggest mycoplasmas formed by [[De-evolution|degenerative evolution]] from the [[Gram-positive bacteria|gram-positive]] [[eubacteria]]l group that includes ''[[bacilli]]'', ''[[streptococci]]'', and ''[[lactobacilli]]''.<ref name=Waites/><ref name=Weisburg/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = Mycoplasma pneumoniae protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> ''M. pneumoniae'' is a member of the [[Mycoplasmataceae]] family and [[Mycoplasmatales]] order.<ref name=Waites/> | | *The term ''Mycoplasma'' (“mykes”, meaning fungus and “plasma”, meaning formed) is derived from the fungal-like growth of some mycoplasma species.<ref name=Waites/> |
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| ==Cell biology==
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| | ==Cell Biology== |
| [[Image:Mycoplasma pneumoniae cells attached to ciliated mucosal cells.jpeg|500px|thumb|left| A) Filamentous ''Mycoplasma pneumoniae'' cells B) ''M. pneumoniae'' cells (M) attached to ciliated mucosal cells by the attachment organelle (indicated by arrow)]]{{clear right}} | | [[Image:Mycoplasma pneumoniae cells attached to ciliated mucosal cells.jpeg|500px|thumb|left| A) Filamentous ''Mycoplasma pneumoniae'' cells B) ''M. pneumoniae'' cells (M) attached to ciliated mucosal cells by the attachment organelle (indicated by arrow)]]{{clear right}} |
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| Mycoplasmas, the smallest [[self-replicating]] organisms, are [[parasitic]] species that lack a cell wall and [[periplasmic space]], have reduced [[genome]]s, and limited [[metabolic]] activity.<ref name=Waites/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name=Dallo>S. Dallo, and J. Baseman "Intracellular DNA replication and long-term survival of pathogenic mycoplasmas" ''Microb. Pathog.'' 2000; 29, 301–309. {{10.1006/mpat.2000.0395}}</ref> ''Mycoplasma pneumoniae'' cells have an elongated shape that is approximately 1-2 µm in length and 0.1–0.2 µm in width. The extremely small cell size means they are incapable of being examined by [[light microscopy]]; a [[stereomicroscope]] is required for viewing the [[Morphology (biology)|morphology]] of ''M. pneumoniae'' [[Colony (biology)|colonies]], which are usually less than 100 µm in length.<ref name=Waites/> The inability to synthesize a [[peptidoglycan cell wall]] is due to the absence of [[gene]]s encoding its formation and results in an increased importance in maintenance of [[osmotic]] stability to avoid [[desiccation]].<ref name=Waites/> The lack of a cell wall also calls for increased support of the [[cell membrane]], which includes a rigid [[cytoskeleton]] composed of an intricate [[protein]] network and, potentially, an [[extracellular]] [[Capsule (microbiology)|capsule]] to facilitate [[adhesion (medicine)|adherence]] to the [[host cell]].<ref name=Waites>{{cite journal | last1 = Ken | first1 = | last2 = Waites | first2 = B | last3 = Deborah | first3 = F. Talkington | year = 2004 | title = ''Mycoplasma pneumoniae'' and Its Role as a Human Pathogen | url = | journal = Clin. Microbiol. Rev | volume = 17 | issue = 4| pages = 697–728 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> ''M. pneumoniae'' are the only [[bacteria]]l cells that possess [[cholesterol]] in their cell membrane (obtained from the host) and possess more genes that encode for membrane [[lipoprotein]] variations than other mycoplasmas,<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> which are thought to be associated with its parasitic lifestyle. ''M. pneumoniae'' cells also possess an attachment [[organelle]], which is used in the [[Bacterial gliding|gliding motility]] of the organism by an unknown mechanism.<ref name=Waites/> | | *Mycoplasmas, the smallest [[self-replicating]] organisms, are bacteria that lack a cell wall and [[periplasmic space]], have reduced [[genome]]s, and limited [[metabolic]] activity.<ref name=Waites/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name=Dallo>S. Dallo, and J. Baseman "Intracellular DNA replication and long-term survival of pathogenic mycoplasmas" ''Microb. Pathog.'' 2000; 29, 301–309. {{10.1006/mpat.2000.0395}}</ref> |
| | | *''Mycoplasma pneumoniae'' cells have an elongated shape that is approximately 1-2 µm in length and 0.1–0.2 µm in width. |
| == Genomics and metabolic reconstruction ==
| | *The extremely small cell size means they are incapable of being examined by [[light microscopy]]; a [[stereomicroscope]] is required for viewing the [[Morphology (biology)|morphology]] of ''M. pneumoniae'' [[Colony (biology)|colonies]], which are usually less than 100 µm in length.<ref name=Waites/> The inability to synthesize a [[peptidoglycan cell wall]] is due to the absence of [[gene]]s encoding its formation and results in an increased importance in maintenance of [[osmotic]] stability to avoid [[desiccation]].<ref name=Waites/> The lack of a cell wall also calls for increased support of the [[cell membrane]], which includes a rigid [[cytoskeleton]] composed of an intricate [[protein]] network and, potentially, an [[extracellular]] [[Capsule (microbiology)|capsule]] to facilitate [[adhesion (medicine)|adherence]] to the [[host cell]].<ref name=Waites>{{cite journal | last1 = Ken | first1 = | last2 = Waites | first2 = B | last3 = Deborah | first3 = F. Talkington | year = 2004 | title = ''Mycoplasma pneumoniae'' and Its Role as a Human Pathogen | url = | journal = Clin. Microbiol. Rev | volume = 17 | issue = 4| pages = 697–728 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> |
| [[Sequencing]] of the ''M. pneumoniae'' genome in 1996 revealed it is 816,394 bp in size.<ref name="Weisburg" /> The genome contains 687 genes that encode for proteins, of which about 56.6% code for essential metabolic [[enzymes]]; notably those involved in [[glycolysis]] and [[organic acid]] [[fermentation]].<ref name="Waites" /><ref name="Weisburg" /><ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> ''M. pneumoniae'' is consequently very susceptible to loss of [[Enzymatic activity|enzymatic function]] by [[gene mutation]]s, as the only buffering systems against functional loss by point mutations are for maintenance of the [[pentose phosphate pathway]] and [[nucleotide]] metabolism.<ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> Loss of function in other pathways is suggested to be compensated by host cell metabolism.<ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> In addition to the potential for loss of pathway function, the reduced genome of ''M. pneumoniae'' outright lacks a number of pathways, including the [[TCA cycle]], [[Electron transport chain|respiratory electron transport chain]], and [[biosynthesis]] pathways for [[amino acids]], [[fatty acids]], [[cholesterol]] and [[purines]] and [[pyrimidines]].<ref name="Waites" /><ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> These limitations make ''M. pneumoniae'' dependent upon import systems to acquire essential building blocks from their host or the environment that cannot be obtained through [[Glycolytic Pathways|glycolytic pathways]].<ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref>
| | *''M. pneumoniae'' are the only [[bacteria]]l cells that possess [[cholesterol]] in their cell membrane (obtained from the host) and possess more genes that encode for membrane [[lipoprotein]] variations than other mycoplasmas, which are thought to be associated with its parasitic lifestyle. ''M. pneumoniae'' cells also possess an attachment [[organelle]], which is used in the [[Bacterial gliding|gliding motility]] of the organism by an unknown mechanism.<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> <ref name=Waites/> |
| Along with energy costly protein and [[RNA]] production, a large portion of energy metabolism is exerted to maintain [[proton gradient]]s (up to 80%) due to the high [[Surface-area-to-volume ratio|surface area to volume ratio]] of ''M. pneumoniae'' cells. Only 12 – 29% of energy metabolism is directed at [[cell growth]], which is unusually low for bacterial cells, and is thought to be an [[adaptation]] of its parasitic lifestyle.<ref name="Wodke" /> Unlike other bacteria, ''M. pneumoniae'' uses the [[codon]] UGA to code for [[tryptophan]] rather than using it as a stop codon.<ref name="Waites" /><ref name="Weisburg" />
| | *The absence of a [[peptidoglycan cell wall]] results in resistance to many [[Antibacterial|antibacterial agents]]. The persistence of ''M. pneumoniae'' infections even after treatment is associated with its ability to mimic [[host cell]] surface composition. |
| | | *On Gram-stain, '''Mycoplasma'' stains pink, i.e. it is Gram-negative by staining. However, it is structurally different from other Gram-negative organisms because it lacks a cell wall. |
| ==Host and reproduction==
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| ''Mycoplasma pneumoniae'' exclusively [[Parasitism|parasitizes]] humans, and has never been isolated as a [[Free-living (disambiguation)|free-living organism]] due to its dependence upon the [[Host (biology)|host]] for survival. [[Reproduction]], therefore, is dependent upon attachment to a host cell. According to Waite and Talkington, specialized reproduction occurs by “[[binary fission]], temporally linked with duplication of its attachment organelle, which migrates to the opposite pole of the cell during replication and before [[nucleoid]] separation”.<ref name=Waites/> [[Mutations]] that affect the formation of the attachment organelle not only hinder [[motility]] and [[cell division]], but also reduce the ability of ''M. pneumoniae'' cells to adhere to the host cell.<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref>
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| ==Pathogenicity==
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| [[Image:Pathogenicity of Mycoplasma pneumoniae in vasculitic-thrombotic disorders.png|500px|thumb|left|Pathogenicity of ''Mycoplasma pneumoniae'' in vasculitic/thrombotic disorders]]{{clear right}}
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| ''Mycoplasma pneumoniae'' [[Parasitism|parasitizes]] the [[respiratory tract]] [[epithelium]] of humans.<ref name=Waites/> Adherence to the respiratory epithelial cells is thought to occur via the attachment organelle, followed by evasion of [[Host (biology)|host]] [[immune system]] by [[intracellular]] localization and adjustment of the [[cell membrane]] composition to mimic the host cell membrane.
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| ===Cytadherence===
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| Adherence of ''M. pneumoniae'' to a host cell (usually a [[respiratory tract]] cell, but occasionally an [[erythrocyte]] or [[Urogenital|urogenital lining]] cell) is the initiating event for [[Pneumonia|pneumonic disease]] and related symptoms.<ref name=Waites/> The specialized attachment [[organelle]] is a [[Polar organelle|polar]], [[Electron density|electron dense]] and elongated cell extension that facilitates [[motility]] and cytadherence to host cells.<ref name=Waites/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> It is composed of a central [[Protein filament|filament]] surrounded by an intra[[cytoplasm]]ic space, along with a number of [[adhesins]] and structural and accessory [[proteins]] localized at the tip of the organelle.<ref name=Waites/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref>
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| A variety of proteins are known to contribute to the formation and functionality of the attachment organelle, including the accessory proteins HMW1–HMW5, P30, P56, and P90 that confer structure and adhesin support, and P1, P30 and P116 which are involved directly in attachment.<ref name=Waites/><ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref><ref name=Baseman>{{cite journal | last1 = Baseman | first1 = J. B. | last2 = Cole | first2 = R. M. | last3 = Krause | first3 = D. C. | last4 = Leith | first4 = D. K. | year = 1982 | title = Molecular basis for cytadsorption of ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 151 | issue = | pages = 1514–1522 }}</ref> This network of proteins participates not only in the initiation of attachment organelle formation and adhesion but also in [[motility]].<ref name=Baseman>{{cite journal | last1 = Baseman | first1 = J. B. | last2 = Cole | first2 = R. M. | last3 = Krause | first3 = D. C. | last4 = Leith | first4 = D. K. | year = 1982 | title = Molecular basis for cytadsorption of ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 151 | issue = | pages = 1514–1522 }}</ref>
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| The P1 adhesin (trypsin-sensitive protein) is a 120 [[kDa]] protein highly clustered on the surface of the attachment organelle tip in [[virulent]] mycoplasmas.<ref name=Waites/><ref name=Baseman>{{cite journal | last1 = Baseman | first1 = J. B. | last2 = Cole | first2 = R. M. | last3 = Krause | first3 = D. C. | last4 = Leith | first4 = D. K. | year = 1982 | title = Molecular basis for cytadsorption of ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 151 | issue = | pages = 1514–1522 }}</ref><ref name=Hahn>{{cite journal | last1 = Hahn | first1 = T.-W | last2 = Willby | first2 = M. J. | last3 = Krause | first3 = D.C. | year = 1998 | title = HMW1 Is Required for Cytadhesin P1 Trafficking to the Attachment Organelle in ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 180 | issue = | pages = 1270–1276 }}</ref> Both the presence of P1 and its concentration on the cell surface are required for the attachment of ''M. pneumoniae'' to the host cell. ''M. pneumoniae'' cells treated with [[monoclonal antibodies]] specific to the [[Immunogenicity|immunogenic]] [[C-terminus]] of the P1 adhesin have been shown to be inhibited in their ability to attach to the host cell surface by approximately 75%, suggesting P1 is a major component in cytadherence.<ref name=Waites/><ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref><ref name=Baseman>{{cite journal | last1 = Baseman | first1 = J. B. | last2 = Cole | first2 = R. M. | last3 = Krause | first3 = D. C. | last4 = Leith | first4 = D. K. | year = 1982 | title = Molecular basis for cytadsorption of ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 151 | issue = | pages = 1514–1522 }}</ref> These antibodies also decreased the ability of the cell to [[Bacterial gliding|glide]] quickly, which may contribute to decreased adherence to the host by hindering their capacity to locate a host cell.<ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref> Furthermore, mutations in P1 or degradation by [[trypsin]] treatment yield avirulent ''M. pneumoniae'' cells.<ref name=Waites/> Loss of proteins in the [[cytoskeleton]] involved in the localization of P1 in the tip structure, such as HMW1–HMW3, also cause [[Avirulent|avirulence]] due to the lack of adhesin clustering.<ref name=Baseman>{{cite journal | last1 = Baseman | first1 = J. B. | last2 = Cole | first2 = R. M. | last3 = Krause | first3 = D. C. | last4 = Leith | first4 = D. K. | year = 1982 | title = Molecular basis for cytadsorption of ''Mycoplasma pneumoniae'' | url = | journal = J. Bacteriol | volume = 151 | issue = | pages = 1514–1522 }}</ref><ref name=Hahn/> Another protein considered to play an important role in cytadherence is P30, as ''M. pneumoniae'' cells with mutations in this protein or that have had [[antibodies]] raised against P30 are incapable of adhering to host cells.<ref name=Waites/><ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref> P30 is not involved in the localization of P1 in the tip structure since P1 is trafficked to the attachment organelle in P30 mutants, but rather it may function as a [[Receptor (biochemistry)|receptor]]-binding accessory adhesin.<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name=Hahn/> P30 mutants also display distinct [[Morphology (biology)|morphological]] features such as multiple [[Lobe (anatomy)|lobes]] and a rounded shape as opposed to elongated, which suggests P30 may interact with the cytoskeleton during formation of the attachment organelle.<ref name=Romero-Arroyo>{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref>
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| A number of [[eukaryotic]] cell surface components have been implicated in the adherence of ''M. pneumoniae'' cells to the respiratory tract [[epithelium]]. Among them are [[Glycoconjugates|sialoglycoconjugates]], sulfated [[glycolipids]], [[glycoproteins]], [[fibronectin]], and [[neuraminic acid]] receptors.<ref name=Waites/><ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref><ref name= Sobeslavsky>{{cite journal | last1 = Sobeslavsky | first1 = B. Prescott | last2 = Chanock | first2 = R. M. | title = Adsorption of ''Mycoplasma pneumoniae'' to Neuraminic Acid Receptors of Various Cells and Possible Role in Virulence | url = | journal = J. Bacteriol | volume = 96 | issue = | pages = 695–705 }}</ref> [[Lectins]] on the surface of the bacterial cells are capable of binding [[oligosaccharide]] chains on glycolipids and glycoproteins to facilitate attachment, in addition to the proteins TU and [[Pyruvate dehydrogenase|pyruvate dehydrogenase E1 β]], which bind to fibronectin.<ref name=Waites/><ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref>
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| [[Image:Schematic of the phosphorylated proteins in the attachment organelle in Mycoplasma pneumoniae.jpeg|500px|thumb|left|Schematic of the phosphorylated proteins in the attachment organelle of ''Mycoplasma pneumoniae'']]{{clear left}}
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| ===Intracellular localization===
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| ''Mycoplasma pneumoniae'' is known to evade host [[immune system]] detection, [[Antibiotic resistance|resist antibiotic treatment]], and cross [[mucosal]] barriers, which may be due to its ability to fuse with host cells and survive [[intracellular]]ly.<ref name=Waites/><ref name=Dallo>{{cite journal | last1 = Dallo | first1 = S. | last2 = Baseman | first2 = J. | year = 2000 | title = Intracellular DNA replication and long-term survival of pathogenic mycoplasmas | url = | journal = Microb. Pathog | volume = 29 | issue = | pages = 301–309 | doi = 10.1006/mpat.2000.0395 }}</ref> In addition to the close physical proximity of ''M. pneumoniae'' and host cells, the lack of [[cell wall]] and peculiar [[cell membrane]] components, like [[cholesterol]], may facilitate fusion (1). Internal localization may produce [[Chronicity|chronic]] or latent infections as ''M. pneumoniae'' is capable of persisting, synthesizing [[DNA]], and [[Self-replicating|replicating]] within the host cell even after treatment with antibiotics.<ref name=Dallo>{{cite journal | last1 = Dallo | first1 = S. | last2 = Baseman | first2 = J. | year = 2000 | title = Intracellular DNA replication and long-term survival of pathogenic mycoplasmas | url = | journal = Microb. Pathog | volume = 29 | issue = | pages = 301–309 | doi = 10.1006/mpat.2000.0395 }}</ref> The exact mechanism of intracellular localization is unknown, however the potential for cytoplasmic sequestration within the host explains the difficulty in completely eliminating ''M. pneumoniae'' [[infection]]s in afflicted individuals.<ref name=Waites/>
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| ===Immune response===
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| In addition to evasion of host immune system by intracellular localization, ''M. pneumoniae'' can change the composition of its cell membrane to mimic the host cell membrane and avoid detection by [[Lymphocyte|immune system cells]]. ''M. pneumoniae'' cells possess a number of protein and glycolipid [[antigens]] that elicit [[immune response]]s, but variation of these surface antigens would allow the infection to persist long enough for ''M. pneumoniae'' cells to fuse with host cells and escape detection. The similarity between the compositions of ''M. pneumoniae'' and human cell membranes can also result in [[autoimmune response]]s in several organs and tissues.<ref name=Waites/>
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| ===Cytotoxicity and organismal effects===
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| The main [[Cytotoxicity|cytotoxic]] effect of ''M. pneumoniae'' is local disruption of tissue and cell structure along the respiratory tract epithelium due to its close proximity to host cells. Attachment of the bacteria to host cells can result in loss of [[cilia]], a reduction in [[metabolism]], [[biosynthesis]], and import of [[macromolecules]], and, eventually, infected cells may be shed from the [[epithelial]] lining.<ref name=Waites/> The [[organism]] is not known to produce any [[exotoxins]], but formation of [[hydrogen peroxide]] is a key [[virulence factor]] in ''M. pneumoniae'' infections.<ref name=Waites/> Attachment of ''M. pneumoniae'' to [[erythrocytes]] permits [[diffusion]] of hydrogen peroxide from the bacteria to the host cell without [[detoxification]] by [[catalase]] or [[peroxidase]], which can injure the host cell by reducing [[glutathione]], damaging [[lipid]] membranes and causing [[protein denaturation]].<ref name=Waites/><ref name= Sobeslavsky>{{cite journal | last1 = Sobeslavsky | first1 = B. Prescott | last2 = Chanock | first2 = R. M. | title = Adsorption of ''Mycoplasma pneumoniae'' to Neuraminic Acid Receptors of Various Cells and Possible Role in Virulence | url = | journal = J. Bacteriol | volume = 96 | issue = | pages = 695–705 }}</ref> Local damage may also be a result of [[lactoferrin]] acquisition and subsequent [[hydroxyl radical]], [[superoxide anion]] and [[peroxide]] formation.<ref name=Waites/> The cytotoxic effects of ''M. pneumoniae'' infections translate into common symptoms like [[coughing]] and lung [[irritation]] that may persist for months after infection has subsided. Local [[inflammation]] and hyperresponsiveness by infection induced [[cytokine]] production has been associated with chronic conditions such as [[bronchial asthma]] and has also been linked to progression of symptoms in individuals with [[cystic fibrosis]] and [[COPD]].<ref name=Waites/>
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| {{see also|Asthma-related microbes}}
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| ==Epidemiology== | | == Genomics== |
| The incidence of disease does not appear be related to season or geography, however infection tends to occur more frequently during the summer and fall months when other respiratory [[pathogens]] are less prevalent. Reinfection and [[epidemic]] cycling is thought to be a result of P1 [[adhesin]] subtype variation.<ref name=Waites/> Approximately 40% of community-acquired [[pneumonia]] is due to ''M. pneumoniae'' infections, with children and elderly individuals being most [[Susceptible individual|susceptible]], however no personal risk factors for acquiring ''M. pneumoniae'' induced pneumonia have been determined.<ref name=Waites/><ref name=Daxboeck>{{cite journal | last1 = Daxboeck | first1 = F. | last2 = Krause | first2 = R. | last3 = Wenisch | first3 = C. | year = 2003 | title = Laboratory diagnosis of ''Mycoplasma pneumoniae'' infection | url = | journal = Clin. Microbiol. Infect | volume = 9 | issue = | pages = 263–273 | doi=10.1046/j.1469-0691.2003.00590.x}}</ref> [[Transmission (medicine)|Transmission]] of ''M. pneumoniae'' can only occur through close contact and exchange of [[aerosols]] by coughing due to the increased susceptibility of the [[cell wall]] lacking organism to [[desiccation]]. [[Outbreak]]s of ''M. pneumoniae'' infections tend to occur within groups of people in close and prolonged proximity, including schools, institutions, military bases, and [[households]].<ref name=Waites/>
| | *[[Sequencing]] of the ''M. pneumoniae'' genome in 1996 revealed it is 816,394 bp (approximately 800 kb) in size.<ref name="Weisburg" /> The genome contains 687 genes that encode for proteins, of which about 56.6% code for essential metabolic [[enzymes]]; notably those involved in [[glycolysis]] and [[organic acid]] [[fermentation]].<ref name="Waites" /><ref name="Weisburg" /><ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> |
| | | *''M. pneumoniae'' is consequently very susceptible to loss of [[Enzymatic activity|enzymatic function]] by [[gene mutation]]s, as the only buffering systems against functional loss by point mutations are for maintenance of the [[pentose phosphate pathway]] and [[nucleotide]] metabolism.<ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> |
| ==Symptoms of infection== | | *Loss of function in other pathways is suggested to be compensated by host cell metabolism.<ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> |
| ''M. pneumoniae'' is known to cause a host of symptoms such as [[primary atypical pneumonia]], [[Bronchitis|tracheobronchitis]], and [[Upper respiratory tract infection|upper respiratory tract disease]]. Primary atypical pneumonia is one of the most severe types of manifestation, with tracheobronchitis being the most common symptom and another 15% of cases, usually adults, remain asymptomatic.<ref name=Waites/><ref name=Daxboeck>{{cite journal | last1 = Daxboeck | first1 = F. | last2 = Krause | first2 = R. | last3 = Wenisch | first3 = C. | year = 2003 | title = Laboratory diagnosis of ''Mycoplasma pneumoniae'' infection | url = | journal = Clin. Microbiol. Infect | volume = 9 | issue = | pages = 263–273 | doi=10.1046/j.1469-0691.2003.00590.x}}</ref> Symptomatic infections tend to develop over a period of several days and manifestation of pneumonia can be confused with a number of other bacterial pathogens and conditions that cause pneumonia. Tracheobronchitis is most common in children due to a reduced immune system capacity, and up to 18% of infected children require [[hospitalization]].<ref name=Waites/> Common mild symptoms include [[sore throat]], [[wheezing]] and [[coughing]], [[fever]], [[headache]], [[coryza]], [[myalgia]] and [[Malaise|feelings of unease]], in which symptom intensity and duration can be limited by early treatment with [[antibiotics]]. Rarely, ''M. pneumoniae'' pneumonia results in death due to [[lesions]] and [[ulceration]] of the epithelial lining, [[pulmonary edema]], and [[bronchiolitis obliterans]]. Extrapulmonary symptoms such as autoimmune responses, [[central nervous system]] complications, and [[dermatological]] disorders have been associated with ''M. pneumoniae'' infections in up to 25% of cases.<ref name=Waites/>
| | *In addition to the potential for loss of pathway function, the reduced genome of ''M. pneumoniae'' outright lacks a number of pathways, including the [[TCA cycle]], [[Electron transport chain|respiratory electron transport chain]], and [[biosynthesis]] pathways for [[amino acids]], [[fatty acids]], [[cholesterol]] and [[purines]] and [[pyrimidines]].<ref name="Waites" /><ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> |
| | | *These limitations make ''M. pneumoniae'' dependent upon import systems to acquire essential building blocks from their host or the environment that cannot be obtained through [[Glycolytic Pathways|glycolytic pathways]].<ref name="Romero-Arroyo">{{cite journal | last1 = Romero-Arroyo | first1 = C. E. | last2 = Jordan | first2 = J. | last3 = Peacock | first3 = S. J. | last4 = Willby | first4 = M. J. | last5 = Farmer | first5 = M. A. | last6 = Krause | first6 = D. C. | year = 1994 | title = ''Mycoplasma pneumoniae'' protein P30 is required for cytadherence and associated with proper cell development | url = | journal = J. Bacteriol | volume = 181 | issue = | pages = 1079–1087 | doi = 10.1128/CMR.17.4.697-728.2004 }}</ref><ref name="Wodke">{{cite journal | last1 = Wodke | first1 = J. A. H. | last2 = Puchałka | first2 = J. | last3 = Lluch-Senar | first3 = M. | last4 = Marcos | first4 = J. | last5 = Yus | first5 = E. | last6 = Godinho | first6 = M. | last7 = Gutiérrez-Gallego | first7 = R. | last8 = Serrano | first8 = L. | last9 = Klipp | first9 = E. | last10 = Maier | first10 = T. | title = Dissecting the energy metabolism in ''Mycoplasma pneumoniae'' through genome-scale metabolic modeling | url = | journal = Mol. Syst. Biol | volume = 2010 | issue = | page = 9 | doi = 10.1038/msb.2013.6 }}</ref> |
| ==Diagnosis== | | *Along with energy costly protein and [[RNA]] production, a large portion of energy metabolism is exerted to maintain [[proton gradient]]s (up to 80%) due to the high [[Surface-area-to-volume ratio|surface area to volume ratio]] of ''M. pneumoniae'' cells. Only 12 – 29% of energy metabolism is directed at [[cell growth]], which is unusually low for bacterial cells, and is thought to be an [[adaptation]] of its parasitic lifestyle.<ref name="Wodke" /> Unlike other bacteria, ''M. pneumoniae'' uses the [[codon]] UGA to code for [[tryptophan]] rather than using it as a stop codon.<ref name="Waites" /><ref name="Weisburg" /> |
| [[Diagnosis]] of ''Mycoplasma pneumoniae'' infections is complicated by the delayed onset of [[symptoms]] and the similarity of symptoms to other pulmonary conditions. Often, ''M. pneumoniae'' infections are diagnosed as other conditions and, occasionally, non-[[pathogenic]] mycoplasmas present in the respiratory tract are mistaken for ''M. pneumoniae''.<ref name=Waites/> Historically, diagnosis of ''M. pneumoniae'' infections was made based on the presence of cold [[agglutinins]] and the ability of the infected material to reduce [[tetrazolium]]. Causative diagnosis is dependent upon [[laboratory]] testing, however these methods are more practical in [[epidemiological]] studies than in patient diagnosis.<ref name=Waites/> [[Cell culture|Culture]] tests are rarely used as diagnosic tools; rather [[immunoblotting]], [[Immunofluorescence|immunofluorescent]] staining, hemadsorption tests, tetrazolium reduction, [[metabolic]] inhibition tests, [[serological]] assays, and [[polymerase chain reaction]] (PCR) are used for diagnosis and characterization of [[Bacterial pneumonia|bacterial pneumonic infections]].<ref name=Waites/> PCR is the most rapid and effective way to determine the presence of ''M. pneumoniae'', however the procedure does not indicate the activity or [[Viability selection|viability]] of the cells present.<ref name=Daxboeck>{{cite journal | last1 = Daxboeck | first1 = F. | last2 = Krause | first2 = R. | last3 = Wenisch | first3 = C. | year = 2003 | title = Laboratory diagnosis of ''Mycoplasma pneumoniae'' infection | url = | journal = Clin. Microbiol. Infect | volume = 9 | issue = | pages = 263–273 | doi=10.1046/j.1469-0691.2003.00590.x}}</ref> [[Enzyme immunoassay|EIA]] serological assays are the most common method of ''M. pneumoniae'' detection used in patient diagnosis due to the low cost and relatively short testing time. One drawback of serology is that viable organisms are required, which may overstate the severity of infection.<ref name=Waites/> Neither of these methods, along with others, has been available to medical professionals in a rapid, efficient and inexpensive enough form to be used in routine diagnosis, leading to decreased ability of physicians to diagnose ''M. pneumoniae'' infections.
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| ==Treatment and prevention== | |
| The difficulty in eradicating ''Mycoplasma pneumoniae'' infections is due to the ability of the bacterium to persist within an individual, as well as the lack of cell wall in ''M. pneumoniae'', which renders multiple antibiotics directed at the bacterial cell wall ineffective in treating infections.<ref name=Waites/> ''M. pneumoniae'' therefore displays resistance to antimicrobials such as [[β-lactams]], [[glycopeptides]], [[Sulfonamide (medicine)|sulfonamides]], [[trimethoprim]], [[polymixins]], [[nalidixic acid]], and [[rifampin]].<ref name=Waites/><ref name=Daxboeck>{{cite journal | last1 = Daxboeck | first1 = F. | last2 = Krause | first2 = R. | last3 = Wenisch | first3 = C. | year = 2003 | title = Laboratory diagnosis of ''Mycoplasma pneumoniae'' infection | url = | journal = Clin. Microbiol. Infect | volume = 9 | issue = | pages = 263–273 | doi=10.1046/j.1469-0691.2003.00590.x}}</ref> The majority of antibiotics used to treat ''M. pneumoniae'' infections are targeted at bacterial [[rRNA]] in [[Ribosome|ribosomal]] complexes, including [[macrolides]], [[tetracycline]], [[ketolides]], and [[fluoroquinolone]], many of which can be administered orally.<ref name=Waites/><ref name=Matsuoka >{{cite journal | last1 = Matsuoka | first1 = M. | last2 = Narita | first2 = M. | last3 = Okazaki | first3 = N. | last4 = Ohya | first4 = H. | last5 = Yamazaki | first5 = T. | last6 = Ouchi | first6 = K. | last7 = Suzuki | first7 = I. | last8 = Andoh | first8 = T. | last9 = Kenri | first9 = T. | last10 = Sasaki | first10 = Y. | last11 = Horino | first11 = A. | last12 = Shintani | first12 = M. | last13 = Arakawa | first13 = Y. | last14 = Sasaki | first14 = T. | year = 2004 | title = Characterization and Molecular Analysis of Macrolide-Resistant ''Mycoplasma pneumoniae'' Clinical Isolates Obtained in Japan | url = | journal = Antimicrob. Agents Chemother | volume = 48 | issue = | pages = 4624–4630 | doi = 10.1128/AAC.48.12.4624-4630.2004 }}</ref> Macrolides are capable of reducing hyperresponsiveness and protecting the epithelial lining from [[Oxidative stress|oxidative]] and structural damage, however they are capable only of inhibiting bacteria ([[Bacteriostatic agent|bacteriostatic]]) and are not able to cause bacterial cell death.<ref name=Waites/><ref name=Dallo>{{cite journal | last1 = Dallo | first1 = S. | last2 = Baseman | first2 = J. | year = 2000 | title = Intracellular DNA replication and long-term survival of pathogenic mycoplasmas | url = | journal = Microb. Pathog | volume = 29 | issue = | pages = 301–309 | doi = 10.1006/mpat.2000.0395 }}</ref> The most common macrolides used in the treatment of infected children in Japan are [[erythromycin]] and [[clarithromycin]], which inhibit bacterial protein synthesis by binding [[23S rRNA (guanine745-N1)-methyltransferase|23S rRNA]].<ref name=Matsuoka >{{cite journal | last1 = Matsuoka | first1 = M. | last2 = Narita | first2 = M. | last3 = Okazaki | first3 = N. | last4 = Ohya | first4 = H. | last5 = Yamazaki | first5 = T. | last6 = Ouchi | first6 = K. | last7 = Suzuki | first7 = I. | last8 = Andoh | first8 = T. | last9 = Kenri | first9 = T. | last10 = Sasaki | first10 = Y. | last11 = Horino | first11 = A. | last12 = Shintani | first12 = M. | last13 = Arakawa | first13 = Y. | last14 = Sasaki | first14 = T. | year = 2004 | title = Characterization and Molecular Analysis of Macrolide-Resistant ''Mycoplasma pneumoniae'' Clinical Isolates Obtained in Japan | url = | journal = Antimicrob. Agents Chemother | volume = 48 | issue = | pages = 4624–4630 | doi = 10.1128/AAC.48.12.4624-4630.2004 }}</ref> Administration of antibiotics has been proven to reduce the longevity and intensity of ''M. pneumoniae'' infections in comparison to cases left untreated. Additionally, some high-dose steroid therapies have shown to reverse [[neurological]] effects in children with complicated infections.<ref name=Waites/> Antimicrobial drug resistance rates for ''Mycoplasma pneumoniae'' were determined in clinical specimens and isolates obtained during 2011–2012 in Ontario, Canada. Of 91 ''M. pneumoniae'' drug-resistant specimens, 11 (12.1%) carried nucleotide mutations associated with [[macrolide]] resistance in the [[23S ribosomal RNA|23S rRNA]] gene. None of the ''M. pneumoniae'' specimens were resistant to [[fluoroquinolone]]s or [[tetracycline]]s.<ref>{{cite journal | last1 = Eshaghi | first1 = A | last2 = Memari | first2 = N | last3 = Tang | first3 = P | last4 = Olsha | first4 = R | last5 = Farrell | first5 = DJ | last6 = Low | first6 = DE | display-authors = 6 | last7 = et al | title = Macrolide-resistant Mycoplasma pneumoniae in humans, Ontario, Canada, 2010–2011 | url = | journal = Emerg Infect Dis | volume = 19| issue = | page = | doi = 10.3201/eid1909.121466 }}</ref>
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| [[Vaccine]] design for ''M. pneumoniae'' has been focused primarily on prevention of host cell attachment, which would prevent initiation of [[cytotoxicity]] and subsequent symptoms.<ref name=Waites/> To date, vaccines targeted at the P1 [[adhesin]] have shown no reduction in the onset of infection, and some vaccine trials resulted in worsened symptoms due to immune system [[Sensitization (immunology)|sensitization]].<ref name=Waites/> Introduction of [[peptides]] that block adhesion receptors on the surface of the host cell may also be able to prevent attachment of ''M. pneumoniae''.<ref name=Drasbek>{{cite journal | last1 = Drasbek | first1 = M. | last2 = Christiansen | first2 = G. | last3 = Drasbek | first3 = K. R. | last4 = Holm | first4 = A. | last5 = Birkelund | first5 = S. | year = 2007 | title = Interaction between the P1 protein of ''Mycoplasma pneumoniae'' and receptors on HEp-2 cells | url = | journal = Microbiology | volume = 153 | issue = | pages = 3791–3799 | doi = 10.1099/mic.0.2007/010736-0 }}</ref>
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| Transmission of ''Mycoplasma pneumoniae'' infections is difficult to limit because of the several day period of infection before symptoms appear.<ref name=Meyers>{{cite journal | last1 = Meyers | first1 = L. A. | last2 = Newman | first2 = M. E. J. | last3 = Martin | first3 = M. | last4 = Schrag | first4 = S. | title = Applying Network Theory to Epidemics: Control Measures for ''Mycoplasma pneumoniae'' Outbreaks | url = | journal = Emerg. Infect. Dis. | volume = 9 | issue = | pages = 204–210 | doi=10.3201/eid0902.020188}}</ref> The lack of proper diagnostic tools and effective treatment for the bacterium also contribute to the outbreak of infection.<ref name=Meyers>L. A. Meyers, M. E. J. Newman, M. Martin, and S. Schrag "Applying Network Theory to Epidemics: Control Measures for ''Mycoplasma pneumoniae'' Outbreaks" Emerg. Infect. Dis. 9, 204–210.</ref> Using [[Network theory in risk assessment|network theory]], Meyers ''et al''. analyzed the transmission of ''M. pneumoniae'' infections and developed control strategies based on the created model. They determined that [[Cohort (statistics)|cohorting]] is less effective due to the long [[incubation period]], and so the best method of prevention is to limit [[caregiver]]-patient interactions and reduce the movement of caregivers to multiple [[Hospital#Departments|wards]].<ref name=Meyers>{{cite journal | last1 = Meyers | first1 = L. A. | last2 = Newman | first2 = M. E. J. | last3 = Martin | first3 = M. | last4 = Schrag | first4 = S. | title = Applying Network Theory to Epidemics: Control Measures for ''Mycoplasma pneumoniae'' Outbreaks | url = | journal = Emerg. Infect. Dis. | volume = 9 | issue = | pages = 204–210 | doi=10.3201/eid0902.020188}}</ref>
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| ==See also==
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| * [[Mycoplasma]]
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| * [[Mollicutes]]
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| * [[Bacterial pneumonia]]
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
| ''This article incorporates public domain text from the CDC as cited.''
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| == Further reading ==
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| {{refbegin|2}}
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| *{{cite journal | author=Baseman J. B. |title=Interplay between Mycoplasma Surface Proteins, Airway Cells, and the Protean Manifestations of Mycoplasma-mediated Human Infections |journal=American Journal of Respiratory and Critical Care Medicine |volume=154 |pages= 137–144 |year= 1996 |doi= 10.1164/ajrccm/154.4_Pt_2.S137 }}
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| *{{cite journal | author=Razin S., Yogev D., Naot Y. |title=Molecular biology and pathogenicity of mycoplasmas |journal=Microbiol. Mol. Biol. Rev. |volume= 62 |issue= 4 |pages= 1094–156 |year= 1998 |pmid= 9841667 |pmc=98941}}
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| *{{cite journal | author=Kashyap S., Sarkar, M. |title=''Mycoplasma pneumonia'': Clinical features and management |journal= Lung India |volume=27 |issue= 2 |pages= 75–85 |year= 2010 |doi= 10.4103/0970-2113.63611 }}
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| *{{cite journal | author= Narita M. |title=Pathogenesis of neurologic manifestations of ''Mycoplasma pneumoniae'' infection |journal= Pediatr Neurol. |volume=41 |issue= 3 |pages= 159–166 |year= 2009 |pmid= 19664529 |doi= 10.1016/j.pediatrneurol.2009.04.012 }}
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| *{{cite journal | author= Ferwerda A., Moll H. A., de Groot R. |title=Respiratory tract infections by Mycoplasma pneumoniae in children: a review of diagnostic and therapeutic measures |journal= Eur J Pediatr. |volume=160 |issue= 8 |pages= 483–491 |year= 2001 |pmid= 11548186 |doi=10.1007/s004310100775}}
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| *{{cite journal | author= Esposito S., Droghetti R., Bosis S., Claut L. Marchisio P., Principi N. |title=Cytokine secretion in children with acute ''Mycoplasma pneumoniae'' infection and wheeze |journal= Pediatric Pulmonology |volume=34 |issue= 2 |pages= 122–127 |year= 2002 |doi= 10.1002/ppul.10139 }}
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| *{{cite journal | author= Ríos A. M., Mejías A., Chávez-Bueno S., Fonseca-Aten M., Katz K., Hatfield J., Gómez A. M., Jafri H. S., McCracken G. H., Ramilo O., Hardy R. D. |title=Impact of Cethromycin (ABT-773) Therapy on Microbiological, Histologic, Immunologic, and Respiratory Indices in a Murine Model of Mycoplasma pneumoniae Lower Respiratory Infection |journal= Antimicrob Agents Chemother. |volume=48 |issue= 8 |pages= 2897–2904 |year= 2004 |doi= 10.1128/AAC.48.8.2897-2904.2004 }}
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| {{refend}}
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| ==External links==
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| *[http://nar.oxfordjournals.org/content/24/22/4420.full ''Mycoplasma pneumoniae'' genome]
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| {{Gram-positive bacterial diseases}}
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| {{DEFAULTSORT:Mycoplasma Pneumoniae}}
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| [[Category:Mollicutes]]
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| [[Category:Bacteria with sequenced genomes]]
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| [[Category:Pathogenic bacteria]]
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