Mollicutes

{{Short description|Class of bacteria}} {{Automatic taxobox | name = Mollicutes | image = | image_caption = ''Acholeplasma palmae'' | taxon = Mollicutes | authority = Edward and Freundt 1967<ref name=Edward/> | subdivision_ranks = Orders | subdivision = * Acholeplasmatales * Anaeroplasmatales * Haloplasmatales * Mycoplasmatales * Mycoplasmoidales | synonyms = * Culicoidibacteria Neupane et al. 2020 * Erysipelotrichia Ludwig, Schleifer & Whitman 2010 * "Erysipelotrichidae" corrig. Cavalier-Smith 2020 * "Izemaplasma" (sic) Skennerton et al. 2016 * "Izemoplasmatia" corrig. Zheng et al. 2021 * "Paramycetes" Sabin 1941 }}

thumb | right | alt=Corn Stunt Spiroplasma in phloem cells. Thick section (0.4 micrometers) observed in a TEM. Magnified 75,000X. | Corn Stunt Spiroplasma in phloem cells. Thick section (0.4 micrometers) observed in a TEM. Magnified 75,000X. '''Mollicutes''' is a class of bacteria distinguished by the absence of a cell wall and its peptidoglycan.<ref name="Madigan-2015">{{Cite book |last=Madigan |first=Michael T. |title=Brock Biology of Microorganisms |last2=Martinko |first2=John M. |last3=Bender |first3=Kelly S. |last4=Buckley |first4=Daniel H. |last5=Stahl |first5=David A. |publisher=Pearson Education Limited |year=2015 |isbn=978-1-292-01831-7 |edition=14 |location=Boston |pages=66–67}}</ref> The word ''Mollicutes'' is derived from Latin ''{{wikt-lang|la|mollis}}'' 'soft, pliable' and ''{{wikt-lang|la|cutis}}'' 'skin'. Individuals are very small, typically only 0.2–0.3 μm (200–300 nm) in size and have a very small genome size. They vary in form, although most have sterols that make the cell membrane somewhat more rigid. Many move about by gliding, but members of the genus ''Spiroplasma'' are helical and move by twisting. The best-known genus in the Mollicutes is ''Mycoplasma'', though it has been split in 2018 into several genera. Colonies show the typical "fried-egg" appearance.

Mollicutes can be parasitic or saprotrophic. They can be parasites of various animals and plants, living on or in the host's cells. Many cause diseases in humans, attaching to cells in the respiratory or urogenital tracts, particularly species of ''Mycoplasma'' and ''Ureaplasma''. Phytoplasma and ''Spiroplasma'' are plant pathogens associated with insect vectors.

The absence of peptidoglycan makes them naturally resistant to antibiotics such as the beta-lactam antibiotics that target cell wall synthesis. Several species are pathogenic in humans, including ''Mycoplasmoides pneumoniae'', which is an important cause of "walking" pneumonia and other respiratory disorders, and ''Mycoplasmoides genitalium'', which is believed to be involved in pelvic inflammatory diseases. Mollicutes species are among the smallest organisms yet discovered,<ref>{{cite book |author1=Richard L. Sweet |url=https://archive.org/details/infectiousdiseas00swee_0 |title=Infectious Diseases of the Female Genital Tract |author2=Ronald S. Gibbs |publisher=Lippincott Williams & Wilkins, 2009 |year=1985 |isbn=978-0-683-08038-4 |url-access=registration}}</ref> can survive without oxygen, and come in various shapes. For example, ''Md. genitalium'' is flask-shaped (about 300 x 600'' ''nm), while ''Md. pneumoniae'' is more elongated (about 100 x 1000'' ''nm), many Mollicutes species are coccoid. Hundreds of Mollicutes species, mainly those formerly classified in ''Mycoplasma,'' infect animals.<ref name="LarsenHwang2010">{{cite journal |last1=Larsen |first1=Bryan |last2=Hwang |first2=Joseph |year=2010 |title=Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look |journal=Infectious Diseases in Obstetrics and Gynecology |volume=2010 |pages=1–7 |doi=10.1155/2010/521921 |issn=1064-7449 |pmc=2913664 |pmid=20706675 |doi-access=free}}</ref>

Whereas formerly the trivial name "mycoplasma" (plural: "mycoplasmas") has commonly denoted any member of the class Mollicutes, it now in scientific classification refers exclusively to a member of the genus ''Mycoplasma''. A reorganization of ''Mycoplasma'' in 2018 has moved many species out of the genus, making this old interpretation once again useful. The smallest taxonomic node that covers all members of pre-2018 ''Mycoplasma'' is Mollicutes.<ref>{{cite journal |last1=Gupta |first1=R.S. |last2=Sawnani |first2=S. |last3=Adeolu |first3=M. |last4=Alnajar |first4=S. |last5=Oren |first5=A. |year=2018 |title=Phylogenetic framework for the phylum Tenericutes based on genome sequence data: proposal for the creation of a new order Mycoplasmoidales ord. nov., containing two new families Mycoplasmoidaceae fam. nov. and Metamycoplasmataceae fam. nov. harbouring Eperythrozoon, Ureaplasma and five novel genera |journal=Antonie van Leeuwenhoek |volume=111 |issue=9 |pages=1583–1630 |doi=10.1007/s10482-018-1047-3 |pmid=29556819 |s2cid=254226604}}</ref>

==Origin and evolution to parasitic life== Analysis of the genomes of Mollicutes ("mycoplasmas") gives solid support for the hypothesis that Mollicutes evolved from Gram-positive bacteria by a process of reductive evolution. By adopting a parasitic mode of life with use of nutrients from their hosts, many Mollicutes reduced their genetic material considerably. On the other hand, they lost the genes for many assimilative processes. Thus, ''Mycoplasma'' possibly became the smallest self-replicating organism in nature. ''Mycoplasmoides genitalium'', with 580,000 base pairs, has an especially small genome size. Some phytoplasmas also have a very small genome size. The genera with the smallest genome are considered to be phylogenetically the most "recent" mollicutes.

To maintain their parasitic mode of life the Mollicutes have developed rather sophisticated mechanisms to colonize their hosts and resist the host immune system.<ref>Shmuel Razin, David Yogev and Yehudith Naot [http://mmbr.asm.org/cgi/content/full/62/4/1094 ''Molecular Biology and Pathogenicity of Mycoplasmas'']. Micr. and Molec. Biology Reviews, December '''1998''', pp. 1094–1156, Vol. 62, No. 4</ref>

===Proliferation=== Mollicutes (formerly also called pleuropneumonia-like organisms, PPLO) as well as L-form bacteria (formerly also called L-phase bacteria), both lacking cell walls, do not proliferate by binary fission but by a budding mechanism.<ref>{{Cite journal |last=Martin |first=Hans Herbert |date=2010 |title=L-forms and the unusual formation of progeny in cell wall-less bacteria: Recognizing the old roots of new science |url=https://pubmed.ncbi.nlm.nih.gov/20058000/ |journal=Archives of Microbiology |volume=192 |issue=3 |pages=235-236 |doi=10.1007/s00203-009-0540-5 |pmid=20058000}}</ref> In 1954, this mode of proliferation has been shown by continual observations of live cells using phase-contrast microscopy.<ref>{{Cite journal |last1=Kandler |first1=Gertraud |last2=Kandler |first2=Otto |author-link2=Otto Kandler |date=1954 |others= |title=Untersuchungen über die Morphologie und die Vermehrung der pleuropneumonie-ähnlichen Organismen und der L-Phase der Bakterien. I. Lichtmikroskopische Untersuchungen |trans-title=Studies on morphology and multiplication of pleuropneumonia-like organisms and on bacterial L-phase, I. Light microscopy (now mycoplasmas and L-form bacteria) |url=https://badw.de/fileadmin/members/K/1501/1954-Kandler_Kandler-PPLO-I-English2015-03-11.pdf |journal=Archiv für Mikrobiologie |language= |volume=21 |issue=2 |pages=178–201 |bibcode=1954ArMic..21..178K |doi=10.1007/BF01816378 |pmid=14350641 |s2cid=21257985}}</ref>

Previously, Mollicutes were sometimes considered stable L-form bacteria, but phylogenetic analysis has identified them as bacteria that have lost their cell walls in the course of evolution.<ref name="woese 1980" />

==History of the classification== The classification of the Mollicutes has always been difficult. The individuals are tiny, and being parasites, they have to be cultivated on special media. Until now, many species could not be isolated at all. In the beginning, whether they were fungi, viruses, or bacteria was not clear. Also, the resemblance to L-forms was confusing. At first, all members of the class Mollicutes were generally named "mycoplasma" or pleuropneumonia-like organism (PPLO). Mollicutes other than some members of genus ''Mycoplasma'' were still unidentified. The first species of ''Mycoplasma''/Mollicutes, that could be isolated was ''Mycoplasma mycoides''. This bacterium was cultivated by Nocard and Roux in 1898.<ref name=Hayflick>{{cite journal|author=Hayflick L. & Chanock, R.M.|title=Mycoplasma Species of Man|journal=Bacteriological Reviews|volume=29|issue=2|pages=185–221|year=1965|doi=10.1128/MMBR.29.2.185-221.1965|pmid=14304038 |pmc=441270 |url = http://mmbr.asm.org/cgi/reprint/29/2/185.pdf|doi-access=free}}</ref>

In 1956, D.G. Edward and E.A. Freundt made a first proposal for classifying and naming PPLOs. They left undecided, however, whether they belong to the bacteria (prokaryotes, in 1956 called "Schizomycetes") or to the eukaryotes. As type species (name-giving species) of the PPLOs/mycoplasmas, Edward and Freundt proposed ''Mycoplasma mycoides'', being the causative organism of bovine pleuropneumonia and referring to the pleuropneumonia-like organisms. Until then, ''Mycoplasma mycoides'' was known as ''Asterococcus mycoides'', but later that name was not recognized as valid. In their publication of 1956, they described 15 species of ''Mycoplasma''.<ref>{{cite journal |author=Edward DG, Freundt EA |date=February 1956 |title=The classification and nomenclature of organisms of the pleuropneumonia group |journal=J. Gen. Microbiol. |volume=14 |issue=1 |pages=197–207 |doi=10.1099/00221287-14-1-197 |pmid=13306904 |doi-access=free}}pdf [http://mic.sgmjournals.org/cgi/reprint/14/1/197.pdf]</ref> In 1967 the class Mollicutes, containing the order Mycoplasmatales, was proposed by the Subcommittee on Taxonomy of the Mycoplasmata.<ref name="Edward">{{cite journal|last=Edward|first=D.G.|author2=F.A. Freundt|date=July 1967|title=Proposal for Mollicutes as name of the class established for the order Mycoplasmatales|journal=Int J Syst Bacteriol|volume=17|issue=3|pages=267–268|doi=10.1099/00207713-17-3-267|doi-access=free}}</ref> Now, the name ''Mycoplasma'' should exclusively be used for members of the '''genus''' ''Mycoplasma'', rather than the use as a trivial name for any Mollicute. As the trivial name has been used in literature for a long time, this is yet not always the case.

For classification and nomenclature of Mollicutes, there are special rules, which are maintained by the ''International Committee on Systematics of Prokaryotes (ICSP) Subcommittee on the Taxonomy of Mollicutes'' (formerly the ''International Committee on Systematic Bacteriology (ICSB) Subcommittee on taxonomy of Mycoplasmatales'').<ref name="standards">[http://ijs.sgmjournals.org/cgi/content/full/57/11/2703 ''Revised minimal standards for description of new species of the class Mollicutes (division Tenericutes)''] {{Webarchive|url=https://web.archive.org/web/20100710160820/http://ijs.sgmjournals.org/cgi/content/full/57/11/2703|date=2010-07-10}} PDF [http://ijs.sgmjournals.org/cgi/reprint/45/3/605.pdf]{{Dead link|date=April 2020|bot=InternetArchiveBot|fix-attempted=yes}}; Daniel R. Brown, Robert F. Whitcomb and Janet M. Bradbury (2007) ''Int J Syst Evol Microbiol'' 57 2703–2719; {{doi|10.1099/ijs.0.64722-0}}</ref>

Traditionally, Mollicutes taxonomy has been based on serology and phenotypic characteristics. However, most modern classifications are based on DNA or RNA sequences, especially 16S rRNA sequences<ref name="woese 1980" /> (see Figure).

===Three divisions of the bacteria=== {{main|Bacterial taxonomy}} Traditionally, the taxonomy of bacteria was based on similarities and differences in morphology (Linnaean taxonomy).

In 1962, R.G.E. Murray proposed to divide the "kingdom" (now domain<ref>{{Cite journal |last1=Woese |first1=Carl R. |author-link=Carl Woese |last2=Kandler |first2=Otto |author-link2=Otto Kandler |last3=Wheelis |first3=Mark L. |date=1990 |title=Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=87 |issue=12 |pages=4576–9 |bibcode=1990PNAS...87.4576W |doi=10.1073/pnas.87.12.4576 |pmc=54159 |pmid=2112744|doi-access=free }}</ref>) Bacteria into three divisions (= phyla) on the basis of the cell wall types: # Gram-negative Gracilicutes, with a thin cell wall and little peptidoglycan; # Gram-positive Firmicutes, with a thicker cell wall and more peptidoglycan (the name was later changed in "Firm'''i'''cutes"), and # the "Mollicutes", without a cell wall.<ref>N.E. Gibbons & R.G.E. Murray [http://ijs.sgmjournals.org/cgi/reprint/28/1/1.pdf ''Proposals Concerning the Higher Taxa of Bacteria'']{{Dead link|date=April 2020 |bot=InternetArchiveBot |fix-attempted=yes }} Int J Syst Bacteriol Vol. 28 (1) Jan. 1978, pp. 1–6.</ref>

===The phylum for Mollicutes=== right|thumb|300px| Phylogenetic position of Mollicutes among bacteria, using 16S rRNA sequences.<ref name="Oshima2013">{{Cite journal| pmid = 23966988| pmc = 3743221| year = 2013| last1 = Oshima| first1 = K| title = Genomic and evolutionary aspects of phytoplasmas| journal = Frontiers in Microbiology| volume = 4| page = 230| last2 = Maejima| first2 = K| last3 = Namba| first3 = S| doi = 10.3389/fmicb.2013.00230| doi-access = free}}</ref> The results of Mollicutes phylogenetic analyses have been controversial. Some taxonomists place them in Bacillota, others in Mycoplasmatota. Woese et al. suggested that the Mollicutes might have been derived from different branches of bacteria. They concluded, that the Mollicutes are not a phylogenetically coherent group and therefore do not form a distinct higher level taxon. Instead, they cluster within Gram-positive bacteria of the phylum Bacillota.<ref name="woese 1980">C.R. Woese, J. Maniloff and L.B. Zablen [http://www.pnas.org/content/77/1/494.full.pdf ''Phylogenetic analysis of the mycoplasmas''] Proc. Natl. Acad. Sci. USA Vol. 77, No. 1, pp. 494–498, January 1980</ref> The results of molecular phylogenetic analyses have been partly dependent on the chosen molecular marker, like rRNA, elongation factor or another protein.<ref name="ludwig2005">Ludwig, W. and Schleifer, K.H. [https://books.google.com/books?hl=nl&lr=&id=LA8JHPM3-zsC&pg=PA70 ''Molecular phylogeny of bacteria based on comparative sequence analysis of conserved genes''] Microbial phylogeny and evolution, 2005, p. 70–98.</ref> Phylogenetic trees based on phosphoglycerate kinase (Pgk) amino acid sequences' indicated a monophyletic origin for the Mollicutes within the Bacillota.<ref name="Wolf">{{cite journal|last1=Wolf|first1=Matthias|year=2004|title=Phylogeny of Firmicutes with special reference to Mycoplasma (Mollicutes) as inferred from phosphoglycerate kinase amino acid sequence data|journal=Int J Syst Evol Microbiol|volume=54|pages=871–875|doi=10.1099/ijs.0.02868-0|pmid=15143038|last2=Müller|first2=T|last3=Dandekar|first3=T|last4=Pollack|first4=JD|issue=Pt 3|display-authors=etal|doi-access=free}} DOI 10.1099/ijs.0.02868-0</ref>

An early edition of ''Bergey's Manual of Systematic Bacteriology'' placed class Mollicutes within phylum Bacillota,<ref name="bergeys">[http://www.bergeys.org/outlines/bergeysoutline_5_2004.pdf Taxonomic Outline of the Prokaryotes. Bergey's Manual of Systematic Bacteriology.] {{webarchive|url=https://web.archive.org/web/20091229160912/http://www.bergeys.org/outlines/bergeysoutline_5_2004.pdf |date=2009-12-29 }} Garrity, Bell & Lilburn; Second Edition, Release 5.0 (2004); pp. 140–204. {{doi|10.1007/bergeysoutline200405}}.</ref><ref>K. Johansson and B. Pettersson, ''Taxonomy of Mollicutes'' [https://books.google.com/books?id=WuMVqDapIbEC&pg=PA10 books.google.com] (2002)</ref> whereas in the announced 2nd edition, they are moved to a separate phylum Tenericutes (later renamed Mycoplasmatota).<ref name=NCBI/><ref name="Ludwig2009">Wolfgang Ludwig, Karl-Heinz Schleifer and William B. Whitman (In press, release in '''2009'''). "Revised road map to the phylum Firmicutes". ''In'' P. De Vos ''et al.'' (eds.) ''Bergey's Manual of Systematic Bacteriology'', 2nd ed., vol. 3 (The Firmicutes). Springer-Verlag, New York. {{ISBN|0-387-95041-9}}; [http://www.bergeys.org/outlines/Bergeys_Vol_3_Outline.pdf PDF] {{webarchive|url=https://web.archive.org/web/20100921022410/http://bergeys.org/outlines/Bergeys_Vol_3_Outline.pdf |date=2010-09-21 }}</ref><ref>''Validation of the Publication of New Names and New Combinations ...'' Int. J. Syst. Bacteriol.; July 1984, pp. 355–357</ref> The change is motivated by "their unique phenotypic properties, in particular the lack of rigid cell walls, and the general low support by alternative markers".<ref name="ludwig2005"/> In the ''Taxonomic Outline of Bacteria and Archaea'' (TOBA Release 7.7), March 2007, the Mollicutes are a class in the phylum Bacillota.<ref name="TOBA">Garrity, et al. [http://www.taxonomicoutline.org/ ''The Taxonomic Outline of Bacteria and Archaea''] {{Webarchive|url=https://web.archive.org/web/20130502073028/http://www.taxonomicoutline.org/ |date=2013-05-02 }} (TOBA Release 7.7); March 2007. {{cite journal |url=http://www.taxonomicoutline.org/index.php/toba/article/view/185/217.pdf |title=Taxonomic Outline of Bacteria and Archaea |journal=Taxonomic Outline of Bacteria and Archaea |access-date=2009-08-13 |archive-url=https://web.archive.org/web/20111007150532/http://www.taxonomicoutline.org/index.php/toba/article/view/185/217.pdf |archive-date=2011-10-07 }}</ref>

Up-to-date analysis of the SSU (16S) rRNA puts Mollicutes in Bacillota (see LTP below). GTDB's 120-protein approach does the same (see below).<ref>{{cite journal | pmc=10868615 | date=2024 | last1=Field | first1=C. J. | last2=Bowerman | first2=K. L. | last3=Hugenholtz | first3=P. | title=Multiple independent losses of sporulation and peptidoglycan in the Mycoplasmatales and related orders of the class Bacilli | journal=Microbial Genomics | volume=10 | issue=1 | page=001176 | doi=10.1099/mgen.0.001176 | doi-access=free | pmid=38189216 }}</ref>

=== The 2018 ''Mycoplasma'' split === It has been known since the 1990s that ''Mycoplasma'' includes several groups that were not very related to its type species. Four lineages were defined by 2007.<ref name="pmid17687503">{{cite journal |vauthors=Oshima K, Nishida H | title = Phylogenetic relationships among mycoplasmas based on the whole genomic information | journal = J. Mol. Evol. | volume = 65 | issue = 3 | pages = 249–58 | date = September 2007 | pmid = 17687503 | doi = 10.1007/s00239-007-9010-3 | bibcode = 2007JMolE..65..249O }}</ref>

In 2018, Gupta et al. re-circumscribed the genus ''Mycoplasma'' around ''M. mycoides''. A total of 78 species were removed from ''Mycoplasma'', creating five new genera and a number of higher taxonomic levels. Under this new scheme, a new family Mycoplasmoidaceae was created to correspond to the "pneumoniae" group, with ''M. pneumoniae'' and related species transferred to a new genus ''Mycoplasmoides''. Another new family Metamycoplasmataceae was created to correspond to the "hominis" group. Both families belong to a new order Mycoplasmoitales, distinct from the Mycoplasmatales of ''Mycoplasma''.<ref name=Gupta18>{{cite journal| last1=Gupta|first1=R.S.| last2=Sawnani|first2=S.| last3=Adeolu|first3=M.| last4=Alnajar|first4=S.| last5=Oren|first5=A.| title=Phylogenetic framework for the phylum Tenericutes based on genome sequence data: proposal for the creation of a new order Mycoplasmoidales ord. nov., containing two new families Mycoplasmoidaceae fam. nov. and Metamycoplasmataceae fam. nov. harbouring Eperythrozoon, Ureaplasma and five novel genera| journal=Antonie van Leeuwenhoek| volume=111| issue=9| pages=1583–1630| year=2018| doi=10.1007/s10482-018-1047-3|pmid=29556819 |s2cid=254226604 }}</ref> The taxonomy was accepted by the ICSB with validation list 184 in 2018 and became the correct name. Both List of Prokaryotic names with Standing in Nomenclature (LPSN)<ref name=LPSN1>{{cite web| author=A.C. Parte| url=https://lpsn.dsmz.de/genus/Mycoplasma| title=Mycoplasma| access-date=2022-09-09| publisher=List of Prokaryotic names with Standing in Nomenclature (LPSN)| display-authors=et al.}}</ref> and National Center for Biotechnology Information (NCBI) now use the new nomenclature.<ref name=NCBI1>{{cite web| author = Sayers| url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=2093&lvl=3&keep=1&srchmode=1&unlock| title=Mycoplasma| access-date=2022-09-09| publisher=National Center for Biotechnology Information (NCBI) taxonomy database| display-authors=et al.}}</ref>

Gupta's proposed taxonomy, as expected, moved the medically important "pneumoniae" group out of ''Mycoplasma'' into its own genus. As a result, a number of mycoplasmologists petitioned to the ICSB to reject the name in 2019. They argue that although Gupta's phylogenetic methods were likely solid, the proposed name changes are too sweeping to be practically adopted, citing some principles of the Code such as "name stability".<ref>{{Cite journal |last1=Balish |first1=Mitchell |last2=Bertaccini |first2=A. |last3=Blanchard |first3=A. |last4=Brown |first4=D. |last5=Browning |first5=G.|last6=Chalker |first6=V.|last7=Frey |first7=J.|last8=Gasparich |first8=G.|last9=Hoelzle |first9=L.|last10=Knight |first10=T.|last11=Knox |first11=C.|last12=Chih-Horng |first12=K.|last13=Manso-Silván |first13=L.|last14=May |first14=M.|last15=Pollack |first15=J.D.|last16=Ramírez |first16=A.|last17=Spergser |first17=J.|last18=Taylor-Robinson |first18=D.|last19=Volokhov |first19=D.|last20=Zhao |first20=Y.|date= 2019|title=Recommended rejection of the names Malacoplasma gen. nov., Mesomycoplasma gen. nov., Metamycoplasma gen. nov., Metamycoplasmataceae fam. nov., Mycoplasmoidaceae fam. nov., Mycoplasmoidales ord. nov., Mycoplasmoides gen. nov., Mycoplasmopsis gen. nov. [Gupta, Sawnani, Adeolu, Alnajar and Oren 2018] and all proposed species comb. nov. placed therein |journal=International Journal of Systematic and Evolutionary Microbiology |volume=69 |issue=11 |pages=3650–3653 |doi= 10.1099/ijsem.0.003632 |pmid=31385780 |doi-access=free |hdl=11585/720151 |hdl-access=free }}</ref> Gupta and Oren wrote a rebuttal in 2020, further detailing the pre-existing taxonomic problems.<ref>{{cite journal |last1=Gupta |first1=Radhey S. |last2=Oren |first2=Aharon |title=Necessity and rationale for the proposed name changes in the classification of Mollicutes species. Reply to: 'Recommended rejection of the names Malacoplasma gen. nov., Mesomycoplasma gen. nov., Metamycoplasma gen. nov., Metamycoplasmataceae fam. nov., Mycoplasmoidaceae fam. nov., Mycoplasmoidales ord. nov., Mycoplasmoides gen. nov., Mycoplasmopsis gen. nov. [Gupta, Sawnani, Adeolu, Alnajar and Oren 2018] and all proposed species comb. nov. placed therein', by M. Balish et al. (Int J Syst Evol Microbiol, 2019;69:3650–3653) |journal=International Journal of Systematic and Evolutionary Microbiology |date=1 February 2020 |volume=70 |issue=2 |pages=1431–1438 |doi=10.1099/ijsem.0.003869|doi-access=free |pmid=31971499 }}</ref><ref name="ipsn_gen">{{cite web |title=Genus: Mycoplasmoides |url=https://lpsn.dsmz.de/genus/mycoplasmoides |website=lpsn.dsmz.de |language=en}}; see also LPSN FAQ on [https://lpsn.dsmz.de/text/faq#why-and-how-does-lpsn-assign-the-status-correct-name correct name]</ref> In 2022, the ICSP's Judicial Opinion 122 ruled in favor of the name changes proposed by Gupta, meaning they remain valid under the Prokaryotic Code<ref name=JO122/> (and for the purpose of the LPSN, they remain the "correct names").<ref name="ipsn_gen"/> However, the older names also remain valid; their use remains acceptable under the Code.<ref name=JO122>{{cite journal |last1=Arahal |first1=David R. |last2=Busse |first2=Hans-Jürgen |last3=Bull |first3=Carolee T. |last4=Christensen |first4=Henrik |last5=Chuvochina |first5=Maria |last6=Dedysh |first6=Svetlana N. |last7=Fournier |first7=Pierre-Edouard |last8=Konstantinidis |first8=Konstantinos T. |last9=Parker |first9=Charles T. |last10=Rossello-Mora |first10=Ramon |last11=Ventosa |first11=Antonio |last12=Göker |first12=Markus |title=Judicial Opinions 112–122 |journal=International Journal of Systematic and Evolutionary Microbiology |date=10 August 2022 |volume=72 |issue=8 |doi=10.1099/ijsem.0.005481 |pmid=35947640 |url=https://www.researchgate.net/publication/362626093}}</ref>

Gupta ''et al.'' 2019 performed some uncontroversial sorting of the order Mycoplasmatales.<ref>{{cite journal |last1=Gupta |first1=Radhey S. |last2=Son |first2=Jeen |last3=Oren |first3=Aharon |title=A phylogenomic and molecular markers based taxonomic framework for members of the order Entomoplasmatales: proposal for an emended order Mycoplasmatales containing the family Spiroplasmataceae and emended family Mycoplasmataceae comprising six genera |journal=Antonie van Leeuwenhoek |date=April 2019 |volume=112 |issue=4 |pages=561–588 |doi=10.1007/s10482-018-1188-4|pmid=30392177 }}</ref>

==Phylogeny== The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN)<ref name=LPSN>{{cite web |author=J.P. Euzéby |url=https://lpsn.dsmz.de/phylum/mollicutota |title=Mycoplasmatota |publisher=List of Prokaryotic names with Standing in Nomenclature (LPSN) |access-date=2016-10-21}}</ref> and National Center for Biotechnology Information (NCBI).<ref name=NCBI>{{cite web |author=Sayers |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Undef&id=544448&lvl=3&lin=f&keep=1&srchmode=1&unlock |title=Mycoplasmatota |access-date=2013-03-20| publisher=National Center for Biotechnology Information (NCBI) taxonomy database |display-authors=etal}}</ref>

{| class="wikitable" |- ! colspan=1 | 16S rRNA based LTP_10_2024<ref>{{cite web |title=The LTP |url=https://imedea.uib-csic.es/mmg/ltp/#LTP| access-date=10 December 2024}}</ref><ref>{{cite web |title=LTP_all tree in newick format |url=https://imedea.uib-csic.es/mmg/ltp/wp-content/uploads/ltp/LTP_all_10_2024.ntree |access-date=10 December 2024}}</ref><ref>{{cite web |title=LTP_10_2024 Release Notes |url=https://imedea.uib-csic.es/mmg/ltp/wp-content/uploads/ltp/LTP_10_2024_release_notes.pdf |access-date=10 December 2024}}</ref> ! colspan=1 | 120 marker proteins based GTDB 10-RS226<ref name="about">{{cite web |title=GTDB release 09-RS220 |url=https://gtdb.ecogenomic.org/about#4%7C |website=Genome Taxonomy Database |access-date=10 May 2025}}</ref><ref name="tree">{{cite web |title=bac120_r226.sp_labels |url=https://data.gtdb.ecogenomic.org/releases/release226/226.0/auxillary_files/bac120_r226.sp_labels.tree |website=Genome Taxonomy Database |access-date=10 May 2025}}</ref><ref name="taxon_history">{{cite web |title=Taxon History |url=https://gtdb.ecogenomic.org/taxon_history/ |website=Genome Taxonomy Database |access-date=10 May 2025}}</ref> |- | style="vertical-align:top| {{Clade | style=font-size:90%;line-height:80% |1={{clade |1={{clade |label1=Culicoidibacterales |1=Culicoidibacteraceae }} |2={{clade |1=Turicibacteraceae |label2=Mollicutes |2={{clade |1={{clade |label1=Haloplasmatales |1=Haloplasmataceae♦ }} |2={{clade |1={{clade |label1=Acholeplasmatales♦ |sublabel1=/Anaeroplasmatales(1) |1={{clade |1=Anaeroplasmataceae |2={{clade |1=''Paracholeplasma'' |2=Acholeplasmataceae }} }} }} |label2=(2) |2={{clade |1=Erysipelotrichales [incl. ''Asteroleplasma''♦] |2={{clade |label1=Mycoplasmatales♦ |sublabel1=/Entomoplasmatales |1={{clade |1={{clade |1={{clade |1=''Spiroplasma''~1 |2=Mycoplasmoidaceae }} |2=Mycoplasmataceae [incl. Entomoplasmataceae; Spiroplasmataceae] }} |2=Metamycoplasmataceae [''Mycoplasma''~5] }} }} }} }} }} }} }} }} |  {{clade |style=font-size:90%;line-height:80% |1={{clade |1={{clade |1={{clade |label1=Mycoplasmatota |sublabel1=Mollicutes |1={{clade |1={{clade |1={{Clade |1={{Clade |label1="Aphodocolales"|sublabel1={RF39} |1="Aphodocolaceae" {UBA660} }} |2={{clade |label1=(1) |1={{clade |1={{Clade |label1="Bathyoplasmales" |sublabel1=(sic) {MAG-NZ} |1="Bathyoplasmaceae" (sic) {MAG-NZ} }} |2={{clade |label1="Izemoplasmatales" |1="Izemoplasmataceae" |label2=Acholeplasmatales♦ |sublabel2=/Anaeroplasmatales |2={{clade |1=Anaeroplasmataceae |2={{clade |1=''Paracholeplasma'' {UBA5453} |2=Acholeplasmataceae }} }} }} }} |label2=(2) |2={{clade |1={{clade |1={{clade |label1="Caccosomales" |sublabel1=(sic) {RFN20} |1={{clade |1="Caccosomataceae" {CAG-631} |2={{clade |1="Enterosomataceae" {CAG-288} |2="Enteromonadaceae" {CAG-826} }} }} }} |2=Erysipelotrichales }} |2={{clade |label1=Mycoplasmatales♦ |sublabel1=/Entomoplasmatales |1={{clade |1={{clade |1=''Spiroplasma''_D {VBWQ01} |2=Mycoplasmataceae [incl. Entomoplasmataceae; Spiroplasmataceae] }} |2={{clade |1={{clade |1="''Ca.'' Spiroplasma holothuricola" {MT37} |2=Mycoplasmoidaceae }} |2={{clade |1="Hepatoplasmataceae" |2=Metamycoplasmataceae }} }} }} }} }} }} }} }} |2={{clade|label1=Haloplasmatales|1=Haloplasmataceae}} }} |label2=MOL361|2=Turicibacteraceae }} |2=''Culicoidibacter'' }} |2={{clade|label1="Staphylococcales"|1=Staphylococcaceae}} }} }} |} ♦ Mollicutes

Mycoplasmatota and Mollicutes are not listed in GTDB, but they are recovered as a monophyletic node (marked in cladogram) in RS226 with a low non-parametric bootstrap support of 32%. In RS220, Haloplasmataceae was not grouped in under the same node as the rest of the Mollicutes.

The taxa labels only reflect an approximate match to the current taxonomy. An alternative match has what is labeled "Mollicutes" (or an inner node excluding ''Haloplasma'', as this genus has a peptidoglycan cell wall)<ref>{{cite journal |last1=Field |first1=CJ |last2=Bowerman |first2=KL |last3=Hugenholtz |first3=P |title=Multiple independent losses of sporulation and peptidoglycan in the Mycoplasmatales and related orders of the class Bacilli. |journal=Microbial Genomics |date=January 2024 |volume=10 |issue=1 |doi=10.1099/mgen.0.001176 |doi-access=free |pmid=38189216 |pmc=10868615}}</ref> be "Mycoplasmatota", the node labelled "(1)" as Izemoplasmatia, and the node labelled as "(2)" as Mollicutes sensu stricto.

== Species which infect humans == Species in Mollicutes, other than those listed below, have been recovered from humans, but are assumed to have been contracted from a non-human host. The following species use humans as the primary host (modified for 2018 taxonomy):<ref name="WaitesKatz2005">{{cite journal |last1=Waites |first1=K. B. |last2=Katz |first2=B. |last3=Schelonka |first3=R. L. |year=2005 |title=Mycoplasmas and Ureaplasmas as Neonatal Pathogens |journal=Clinical Microbiology Reviews |volume=18 |issue=4 |pages=757–789 |citeseerx=10.1.1.336.7047 |doi=10.1128/CMR.18.4.757-789.2005 |issn=0893-8512 |pmc=1265909 |pmid=16223956}}</ref> {{div col|colwidth=12em}} * ''Malmycoplasma'' ** ''Ma. penetrans'' * ''Metamycoplasma'' ** ''Me. buccale'' ** ''Me. faucium'' ** ''Me. hominis'' ** ''Me. orale'' ** ''Me. salivarium'' * ''Mycoplasmoides'' ** ''Md. amphoriforme'' ** ''Md. genitalium'' ** ''Md. pirum'' ** ''Md. pneumoniae'' * ''Mycoplasmopsis'' ** ''Mp. fermentans'' *** ''M. incognitus'' ** ''Mp. lipophilum'' ** ''Mp. primatum'' ** ''Mp. spermatophilum'' {{div col end}}

== Pathogenicity == Several species in Mollicutes can cause disease, including ''Md. pneumoniae'', which is an important cause of atypical pneumonia (also known as "walking pneumonia"), and ''Md. genitalium'', which has been associated with pelvic inflammatory diseases. Mycoplasma infections in humans are associated with skin eruptions in 17% of cases.<ref name="Andrews">{{cite book |author1=James, William D. |title=Andrews' Diseases of the Skin: clinical Dermatology |author2=Berger, Timothy G. |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}</ref>{{rp|293}}

=== P1 antigen === The P1 antigen is the primary virulence factor of ''Mycoplasmoides''. P1 is a membrane associated protein that allows adhesion to epithelial cells. The P1 receptor is also expressed on erythrocytes which can lead to autoantibody agglutination from mycobacteria infection.<ref>{{cite book |last1=Parija |first1=Subhash Chandra |title=Textbook of Microbiology & Immunology |publisher=Elsevier Health Sciences |year=2014 |isbn=978-81-312-3624-6}}</ref>

=== Sexually transmitted infections === ''Ureaplasma'', ''Malmycoplasma'', and ''Metamycoplasma'' species are not part of the normal vaginal flora. Some Mollicutes species are spread through sexual contact.<ref name="Sternak">{{cite journal |last1=Ljubin-Sternak |first1=Suncanica |last2=Mestrovic |first2=Tomislav |date=2014 |title=Review: Chlamydia trachonmatis and Genital Mycoplasmias: Pathogens with an Impact on Human Reproductive Health |journal=Journal of Pathogens |volume=2014 |article-number=183167 |doi=10.1155/2014/183167 |pmc=4295611 |pmid=25614838 |quote=The term "mycoplasma" is often used to refer to any members of the class Mollicutes (for the purposes of this review as well), irrespective of the fact whether they truly belong to the genus Mycoplasma |doi-access=free}}</ref> These species have a negative effect on fertility.<ref name="Sternak" /> Mollicutes species colonizing the human genital tract are:<ref name="Sternak" />

* ''U. urealyticum'' * ''Me. hominis'' * ''Md. genitalium'' * ''Ma. penetrans'' * ''Mp. primatum'' (considered nonpathogenic) * ''Mp. spermatophilum'' (considered nonpathogenic)

''Me. hominis'' causes ''male sterility/Genitals inflammation'' in humans.{{citation needed|date=January 2023}}

Mollicutes species have been isolated from women with bacterial vaginosis.<ref name="LarsenHwang2010"/> ''Md. genitalium'' is found in women with pelvic inflammatory disease.<ref>{{Cite journal |last1=Wiesenfeld |first1=Harold C. |last2=Manhart |first2=Lisa E. |date=2017-07-15 |title=Mycoplasma genitalium in Women: Current Knowledge and Research Priorities for This Recently Emerged Pathogen |journal=The Journal of Infectious Diseases |volume=216 |issue=suppl_2 |pages=S389–S395 |doi=10.1093/infdis/jix198 |issn=1537-6613 |pmc=5853983 |pmid=28838078}}</ref> In addition, infection is associated with increased risk of cervicitis, infertility, preterm birth, and spontaneous abortion.<ref name="LisRowhani-Rahbar2015">{{cite journal |last1=Lis |first1=R. |last2=Rowhani-Rahbar |first2=A. |last3=Manhart |first3=L. E. |year=2015 |title=Mycoplasma genitalium Infection and Female Reproductive Tract Disease: A Meta-Analysis |journal=Clinical Infectious Diseases |volume=61 |issue=3 |pages=418–426 |doi=10.1093/cid/civ312 |issn=1058-4838 |pmid=25900174 |doi-access=free |hdl-access=free |hdl=1773/26479}}</ref> ''Mycoplasmoides genitalium'' has developed resistance to some antibiotics.<ref>{{Cite journal |last1=Mitjà |first1=Oriol |last2=Asiedu |first2=Kingsley |last3=Mabey |first3=David |date=13 February 2013 |title=2013 Yaws Seminar |url=https://www.who.int/yaws/2013_Yaws_seminar_Lancet.pdf?ua=1&ua=1 |format=PDF |journal=Lancet |publisher=The Lancet |volume=381 |issue=9868 |pages=763–73 |doi=10.1016/S0140-6736(12)62130-8 |pmid=23415015 |s2cid=208791874 |access-date=28 March 2020 |via=World Health Organization}}</ref>

==== Infant disease ==== Low birth-weight, preterm infants are susceptible to ''Ureaplasma'', ''Malmycoplasma'', and ''Metamycoplasma'' infections. ''Malmycoplasma'' and ''Metamycoplasma'' species are associated with infant respiratory distress syndrome, bronchopulmonary dysplasia, and intraventricular hemorrhage in preterm infants.<ref name="LarsenHwang2010" />

=== Links to cancer === Several species in Mollicutes are frequently detected in different types of cancer cells.<ref name="pmid 11819772">{{cite journal |vauthors=Huang S, Li JY, Wu J, Meng L, Shou CC |date=April 2001 |title=Mycoplasma infections and different human carcinomas |journal=World Journal of Gastroenterology |volume=7 |issue=2 |pages=266–269 |doi=10.3748/wjg.v7.i2.266 |pmc=4723534 |pmid=11819772 |doi-access=free}}</ref><ref name="pmid22076306">{{cite journal |author=Sinkovics JG |date=February 2012 |title=Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review) |journal=International Journal of Oncology |volume=40 |issue=2 |pages=305–349 |doi=10.3892/ijo.2011.1248 |pmid=22076306 |doi-access=free}}</ref><ref name="pmid7479753">{{cite journal |vauthors=Tsai S, Wear DJ, Shih JW, Lo SC |date=October 1995 |title=Mycoplasmas and oncogenesis: Persistent infection and multistage malignant transformation |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=92 |issue=22 |pages=10197–10201 |bibcode=1995PNAS...9210197T |doi=10.1073/pnas.92.22.10197 |pmc=40763 |pmid=7479753 |doi-access=free}}</ref> These species are:

* ''Mp. fermentans''<ref name="pmid 11819772" /><ref name="pmid22076306" /><ref name="pmid7479753" /><ref name="pmid 11575494">{{cite journal |author=Cimolai N |date=August 2001 |title=Do mycoplasmas cause human cancer? |journal=Canadian Journal of Microbiology |volume=47 |issue=8 |pages=691–697 |doi=10.1139/w01-053 |pmid=11575494}}</ref><ref name="pmid18059017">{{cite journal |vauthors=Jiang S, Zhang S, Langenfeld J, Lo SC, Rogers MB |date=May 2008 |title=Mycoplasma infection transforms normal lung cells and induces bone morphogenetic protein 2 expression by post-transcriptional mechanisms |journal=Journal of Cellular Biochemistry |volume=104 |issue=2 |pages=580–594 |doi=10.1002/jcb.21647 |pmid=18059017 |s2cid=23871175}}</ref><ref name="pmid16674811">{{cite journal |vauthors=Zhang S, Tsai S, Lo SC |date=May 2006 |title=Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation |journal=BMC Cancer |volume=6 |page=116 |doi=10.1186/1471-2407-6-116 |pmc=1559712 |pmid=16674811 |doi-access=free}}</ref> * ''Md. genitalium''<ref name="pmid19721714">{{cite journal |vauthors=Namiki K, Goodison S, Porvasnik S, Allan RW, Iczkowski KA, Urbanek C, Reyes L, Sakamoto N, Rosser CJ |date=September 2009 |title=Persistent exposure to mycoplasma induces malignant transformation of human prostate cells |journal=PLOS ONE |volume=4 |issue=9 |article-number=e6872 |bibcode=2009PLoSO...4.6872N |doi=10.1371/journal.pone.0006872 |pmc=2730529 |pmid=19721714 |doi-access=free}}</ref> * ''Mesomycoplasma hyorhinis'' (''Ms. hyorhinis'' hereafter)<ref name="pmid 11819772" /><ref name="pmid19721714" /><ref name="pmid 8910637">{{cite journal |vauthors=Chan PJ, Seraj IM, Kalugdan TH, King A |date=November 1996 |title=Prevalence of mycoplasma conserved DNA in malignant ovarian cancer detected using sensitive PCR–ELISA |journal=Gynecologic Oncology |volume=63 |issue=2 |pages=258–260 |doi=10.1006/gyno.1996.0316 |pmid=8910637}}</ref> * ''Ma. penetrans''<ref name="pmid 11819772" /><ref name="pmid22076306" /><ref name="pmid7479753" /><ref name="pmid 11575494" /><ref name="pmid16674811" /> * ''U. urealyticum''<ref>{{cite journal |vauthors=Xiaolei C, Taot H, Zongli S, Hongying Y |year=2014 |title=The role of ureaplasma urealyticum infection in cervical intraepithelial neoplasia and cervical cancer |journal=European Journal of Gynaecological Oncology |volume=35 |issue=5 |pages=571–5 |pmid=25423707}}</ref>

The majority of these Mollicutes species have shown a strong correlation to malignant transformation in mammalian cells ''in vitro''.

==== Infection and host cell transformation ==== The presence of Mollicutes was first reported in samples of cancer tissue in the 1960s.<ref name="pmid7479753" /> Since then, several studies tried to find and prove the connection between Mollicutes and cancer, as well as how the bacterium might be involved in the formation of cancer.<ref name="pmid22076306" /> Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic Mollicutes infections occur gradually and are both morphological and genetic.<ref name="pmid22076306" /> The first visual sign of infection is when the cells gradually shift from their normal form to sickle-shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for solid support to grow and proliferate,<ref>{{Cite journal |last1=Lopes |first1=B. R. P. |last2=Ribeiro |first2=A. G. |last3=Silva |first3=T. F. |last4=Barbosa |first4=L. V. |last5=Jesus |first5=T. I. |last6=Matsuda |first6=B. K. |last7=Costa |first7=M. F. |last8=Toledo |first8=K. A. |date=February 2021 |title=Diagnosis and treatment of HEp-2 cells contaminated with mycoplasma |journal=Brazilian Journal of Biology |volume=81 |issue=1 |pages=37–43 |doi=10.1590/1519-6984.215721 |issn=1678-4375 |pmid=32321065 |doi-access=free |hdl-access=free |hdl=11449/205878}}</ref> as well as the normal contact-dependent inhibition cells.<ref name="pmid7479753" />

==== Possible intracellular mechanisms ====

===== Karyotypic changes related to infections ===== Cells infected with Mollicutes for an extended period of time show significant chromosomal abnormalities. These include the addition of chromosomes, the loss of entire chromosomes, partial loss of chromosomes, and chromosomal translocation. All of these genetic abnormalities may contribute to the process of malignant transformation. Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes, which caused by these genetic abnormalities and include those encoding c-myc, HRAS,<ref name="pmid 11575494" /> and vav.<ref name="pmid22076306" /> The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by Mollicutes, as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation.<ref name="pmid7479753" /> Two genes whose activities are markedly decreased during chronic infections with Mollicutes are the Rb and the p53 tumour suppressor genes.<ref name="pmid22076306" /> Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of ''Mycoplasmopsis pulmonis''.<ref name="pmid = 24172987">{{cite journal |vauthors=Hu X, Yu J, Zhou X, Li Z, Xia Y, Luo Z, Wu Y |date=Jan 2014 |title=A small GTPase-like protein fragment of Mycoplasma promotes tumor cell migration and proliferation in vitro via interaction with Rac1 and Stat3. |url=http://www.spandidos-publications.com/mmr/9/1/173 |journal=Mol Med Rep |volume=9 |issue=1 |pages=173–179 |doi=10.3892/mmr.2013.1766 |pmid=24172987 |url-access=subscription |doi-access=free}}</ref> A major feature that differentiates Mollicutes from other carcinogenic pathogens is that the Mollicutes do not cause the cellular changes by insertion of their own genetic material into the host cell.<ref name="pmid 11575494" /> The exact mechanism by which the bacterium causes the changes is not yet known.{{citation needed|date=January 2023}}

===== Partial reversibility of malignant transformations ===== The malignant transformation induced by Mollicutes species is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time when reversibility is possible varies greatly; it depends primarily on the Mollicutes involved. In the case of ''Mp. fermentans'', the transformation is reversible until around week 11 of infection and starts to become irreversible between weeks 11 and 18.<ref name="pmid7479753" /> If the bacteria are killed using antibiotics<ref name="pmid7479753" /> (i.e. ciprofloxacin<ref name="pmid22076306" /> or Clarithromycin<ref name="pmid15708077">{{cite journal |vauthors=Pehlivan M, Pehlivan S, Onay H, Koyuncuoglu M, Kirkali Z |date=February 2005 |title=Can mycoplasma-mediated oncogenesis be responsible for formation of conventional renal cell carcinoma? |journal=Urology |volume=65 |issue=2 |pages=411–414 |doi=10.1016/j.urology.2004.10.015 |pmid=15708077}}</ref>) before the irreversible stage, the infected cells should return to normal.

==== Connections to cancer ''in vivo'' and future research ==== Epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. ''Md. genitalium'' and ''Ms. hyorhinis'' induce malignant phenotype in benign human prostate cells (BPH-1) that were not tumorigenic after 19 weeks of exposure.<ref name="pmid19721714" />

==== Types of cancer associated ==== Colon cancer: In a study to understand the effects of Mollicutes contamination on the quality of cultured human colon cancer cells, a positive correlation was found between the number of ''Ms. hyorhinis'' cells present in the sample and the percentage of CD133-positive cells (a glycoprotein with an unknown function).<ref name="pmid 20353562">{{cite journal |vauthors=Mariotti E, Gemei M, Mirabelli P, D'Alessio F, Di Noto R, Fortunato G, Del Vecchio L |date=March 2010 |title=The percentage of CD133+ cells in human colorectal cancer cell lines is influenced by Mycoplasma hyorhinis infection |journal=BMC Cancer |volume=10 |pages=120–125 |doi=10.1186/1471-2407-10-120 |pmc=2854114 |pmid=20353562 |doi-access=free}}</ref>

Gastric cancer: Strong evidence indicates the infection of ''Ms. hyorhinis'' contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.<ref name="pmid21062494">{{cite journal |vauthors=Yang H, Qu L, Ma H, Chen L, Liu W, Liu C, Meng L, Wu J, Shou C |date=November 2010 |title=Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells |journal=BMC Gastroenterology |volume=10 |pages=132–140 |doi=10.1186/1471-230X-10-132 |pmc=2993648 |pmid=21062494 |doi-access=free}}</ref>

Lung cancer: Studies on lung cancer have supported the belief that more than a coincidental positive correlation exists between the appearance of Mollicutes strains in patients and the infection with tumorigenesis.<ref name="pmid21999143">{{cite journal |vauthors=Apostolou P, Tsantsaridou A, Papasotiriou I, Toloudi M, Chatziioannou M, Giamouzis G |date=October 2011 |title=Bacterial and fungal microflora in surgically removed lung cancer samples |journal=Journal of Cardiothoracic Surgery |volume=6 |page=137 |doi=10.1186/1749-8090-6-137 |pmc=3212932 |pmid=21999143 |doi-access=free}}</ref>

Prostate cancer: p37, a protein encoded for by ''Ms. hyorhinis'', has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and gene expression of the cells to change, causing them to become a more aggressive phenotype.<ref name="pmid21663671">{{cite journal |vauthors=Urbanek C, Goodison S, Chang M, Porvasnik S, Sakamoto N, Li CZ, Boehlein SK, Rosser CJ |date=June 2011 |title=Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer |journal=BMC Cancer |volume=11 |issue=1 |pages=233–238 |doi=10.1186/1471-2407-11-233 |pmc=3129326 |pmid=21663671 |doi-access=free}}</ref>

Renal cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mollicutes sp. compared with the healthy control group. This suggests Mollicutes may play a role in the development of RCC.<ref name="pmid15708077" />

== Laboratory contaminant == Mollicutes species are often found in research laboratories as contaminants in cell culture. Mollicutes cell culture contamination occurs due to contamination from individuals or contaminated cell culture medium ingredients. A 2002 report lists ''Me. orale'', ''Ms. hyorhinis'', ''Mp. arginini'', ''Mp. fermentans'', ''Me. hominis'', and ''Acholeplasma laidlawii'' as the most common contaminants.<ref>{{cite journal |author1=Drexler HG |author2=Uphoff CC |date=2002 |title=Mycoplasma contamination of cell cultures: Incidence, sources, effects, detection, elimination, prevention |journal=Cytotechnology |volume=39 |issue=2 |pages=75–90 |doi=10.1023/A:1022913015916 |pmc=3463982 |pmid=19003295}}</ref> Mollicutes cells are physically small – less than 1  μm, so are difficult to detect with a conventional microscope.{{citation needed|date=April 2021}}

Mollicutes may induce cellular changes, including chromosome aberrations, changes in metabolism, and cell growth. Severe Mollicutes infections may destroy a cell line. Detection techniques include DNA probe, enzyme immunoassays, PCR, plating on sensitive agar, and staining with a DNA stain including DAPI or Hoechst.<ref>{{cite book |last=Razin |first=S |url=https://www.ncbi.nlm.nih.gov/books/NBK7637/ |title=Mycoplasmas |date=2001 |publisher=The University of Texas Medical Branch at Galveston |isbn=978-0-9631172-1-2 |pmid=21413254 |access-date=8 July 2021 |via=National Center for Biotechnology Information, U.S. National Library of Medicine}}</ref>

An estimated 11–15% of U.S. laboratory cell cultures are contaminated with Mollicutes. A Corning study showed that half of U.S. scientists did not test for Mollicutes contamination in their cell cultures. The study also stated that, in former Czechoslovakia, 100% of cell cultures that were not routinely tested were contaminated while only 2% of those routinely tested were contaminated (study p. 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for Mollicutes, the actual contamination rate may be higher. European contamination rates are higher and that of other countries are higher still (up to 80% of Japanese cell cultures).<ref name="Corning">{{cite news |author=John Ryan |year=2008 |title=Understanding and Managing Cell Culture Contamination |url=http://catalog2.corning.com/Lifesciences/media/pdf/cccontamination.pdf |archive-url=https://web.archive.org/web/20110708193101/http://catalog2.corning.com/Lifesciences/media/pdf/cccontamination.pdf |archive-date=8 July 2011 |access-date=4 August 2010 |publisher=Corning Incorporated |page=24}}</ref> About 1% of published Gene Expression Omnibus data may have been compromised.<ref name="Astarloa: 2009: BT">{{cite journal |vauthors=Aldecoa-Otalora E, Langdon W, Cunningham P, Arno MJ |date=December 2009 |title=Unexpected presence of mycoplasma probes on human microarrays |journal=BioTechniques |volume=47 |issue=6 |pages=1013–5 |doi=10.2144/000113271 |pmid=20047202 |doi-access=free}}</ref><ref name="wlangdon">[http://bioinformatics.essex.ac.uk/users/wlangdon/rnanet/scatter.html#1570561_at.pm1,1570561_at.pm3 Link] {{Webarchive|url=https://web.archive.org/web/20120330212013/http://bioinformatics.essex.ac.uk/users/wlangdon/rnanet/scatter.html#1570561_at.pm1,1570561_at.pm3|date=30 March 2012}} into RNAnet showing contamination of GEO. Press plot and drag blue crosshairs to expose links to description of experiments on human RNA samples</ref> Several antibiotic-containing formulations of antimycoplasmal reagents have been developed over the years.

==References== {{Reflist|25em}}

==External links== {{MeSH name|Mollicutes}}

Category:Mollicutes Category:Bacteria classes