Mycoplasma

Etymology

The term "mycoplasma", from the Greek μύκης, mykes (fungus) and πλάσμα, plasma (formed), was first used by Albert Bernhard Frank in 1889 to describe an altered state of plant cell cytoplasm resulting from infiltration by fungus-like microorganisms. Julian Nowak later proposed the name mycoplasma for certain filamentous microorganisms imagined to have both cellular and acellular stages in their lifecycles, which could explain how they were visible with a microscope, but passed through filters impermeable to other bacteria.

Later, the name for these mycoplasmas was pleuropneumonia-like organisms (PPLO), broadly referring to organisms similar in colonial morphology and filterability to the causative agent (a Mycoplasma species) of contagious bovine pleuropneumonia. At present, all these organisms are classified as Mollicutes, and the term Mycoplasma solely refers to the genus. removed uncited section The lack of a cell wall conveys some unique properties of mycoplasmas such as sensitivity to osmotic shock and detergents, resistance to penicillin and other beta-lactam antibiotics, and formation of fried-egg shaped colonies. Sections of mycoplasmas reveal that their cells are essentially built of three organelles: the cell membrane, ribosomes, and a circular double-stranded DNA tightly packed molecule. Their mode of replication is no different from that of other prokaryotes dividing by binary fission. For binary fission to happen, cytoplasmic division must fully synchronize with genome replication and in mycoplasma, cytoplasmic replication lags behind genome replication, which ultimately results in the formation of multinucleated filaments.

From in vitro cultivation of mycoplasmas, it has been discovered that they are "fastidious", i.e. difficult to cultivate. The reason for these difficulties for species such as Mycoplasma genitalium and Mycoplasma pneumoniae is the lack of all the genes involved in amino acid synthesis, making them dependent on exogenous supply of amino acids and other nutrients. This dependence on exogenous supplies of fatty acids and cholesterol serves as an advantage to conduct further studies on these organisms. In order to compensate for these deficiencies mycoplasmas are grown on complex media, usually consisting of beef heart infusion, peptone, yeast extract, and serum with various supplements.

Mycoplasmas' lack of a cell wall makes them good models for membrane studies. Due to this reason the availability of these membranes in pure state have enabled their chemical, enzymatic and antigenic characterization. The membrane is made of 60% to 70% protein with the remaining 20% to 30% being lipids.--

Characteristics

Over 100 species were formerly included in the genus Mycoplasma, a member of the class Mollicutes. They are parasites or commensals of humans, animals, and plants. The genus Mycoplasma uses vertebrate and arthropod hosts. Dietary nitrogen availability has been shown to alter codon bias and genome evolution in Mycoplasma and the plant parasites Phytoplasma.

Mycoplasma species are among the smallest free-living organisms (about 0.2–0.3 μm in diameter). They have been found in the pleural cavities of cattle suffering from pleuropneumonia. These organisms are often called MLO (mycoplasma-like organisms) or, formerly, PPLO (pleuropneumonia-like organisms).

Important characteristics

1. Cell wall is absent and plasma membrane forms the outer boundary of the cell.
2. Due to the absence of cell walls these organisms can change their shape and leads to pleomorphism.
3. Lack of nucleus and other membrane-bound organelles.
4. Genetic material is a single DNA duplex and is naked.
5. Ribosomes are 70S type.
6. Possess a replicating disc at one end which assists replication process and also the separation of the genetic materials.
7. Heterotrophic nutrition. Some live as saprophytes but the majority are parasites of plants and animals. The parasitic nature is due to the inability of mycoplasmal bacteria to synthesise the required growth factor.

Cell and colony morphology

Due to the lack of a rigid cell wall, Mycoplasma species (like all Mollicutes) can contort into a broad range of shapes, from round to oblong. They are pleomorphic and therefore cannot be identified as rods, cocci or spirochetes.

Colonies show the typical "fried egg" appearance (about 0.5 mm in diameter).

Reproduction

In 1954, using phase-contrast microscopy, continual observations of live cells have shown that Mycoplasma species ("mycoplasmas", formerly called pleuropneumonia-like organisms, PPLO, now classified as Mollicutes) and L-form bacteria (previously also called L-phase bacteria) do not proliferate by binary fission, but by a uni- or multi-polar budding mechanism. Microphotograph series of growing microcultures of different strains of PPLOs, L-form bacteria and, as a control, a Micrococcus species (dividing by binary fission) have been presented. Additionally, electron microscopic studies have been performed.

Taxonomy

History of taxonomy

Before 1980, Mycoplasma species (often commonly called "mycoplasmas", now classified as Mollicutes) were sometimes considered stable L-form bacteria or even viruses, but phylogenetic analysis has identified them as bacteria that have lost their cell walls in the course of evolution.

Mycoplasmas are unusual among bacteria in that most require sterols for the stability of their cytoplasmic membrane. Sterols are acquired from the environment, usually as cholesterol from the animal host. Mycoplasmas generally possess a relatively small genome of 0. 58-1. 38 megabases, which results in drastically reduced biosynthetic capabilities and explains their dependence on a host. Additionally they use an alternate genetic code in which the codon UGA encodes the amino acid tryptophan instead of the usual stop codon. They have a low GC-content (23–40 mol).-- possible WP:COPYVIO In 1898 Nocard and Roux reported the cultivation of the causative agent of CBPP, which was at that time a grave and widespread disease in cattle herds. The disease is caused by M. mycoides subsp. mycoides SC (small-colony type), and the work of Nocard and Roux represented the first isolation of a mycoplasma species. Cultivation was, and still is difficult because of the complex growth requirements.

These researchers succeeded by inoculating a semipermeable pouch of sterile medium with pulmonary fluid from an infected animal and depositing this pouch intraperitoneally into a live rabbit. After fifteen to twenty days, the fluid inside of the recovered pouch was opaque, indicating the growth of a microorganism. Opacity of the fluid was not seen in the control. This turbid broth could then be used to inoculate a second and third round and subsequently introduced into a healthy animal, causing disease. However, this did not work if the material was heated, indicating a biological agent at work. Uninoculated media in the pouch, after removal from the rabbit, could be used to grow the organism in vitro, demonstrating the possibility of cell-free cultivation and ruling out viral causes, although this was not fully appreciated at the time.-- possible WP:COPYVIO Recent advances in molecular biology and genomics have brought the genetically simple mycoplasmas, particularly M. pneumoniae and its close relative M. genitalium, to a larger audience. The second published complete bacterial genome sequence was that of M. genitalium, which has one of the smallest genomes of free-living organisms. The M. pneumoniae genome sequence was published soon afterwards and was the first genome sequence determined by primer walking of a cosmid library instead of the whole-genome shotgun method. Mycoplasma genomics and proteomics continue in efforts to understand the so-called minimal cell, to catalog the entire protein content of a cell, and generally continue to take advantage of the small genome of these organisms to understand broad biological concepts.--

The medical and agricultural importance of members of the genus Mycoplasma and related genera have led to the extensive cataloging of many of these organisms by culture, serology, and small sub-unit rRNA gene and whole-genome sequencing. A recent focus in the sub-discipline of molecular phylogenetics has both clarified and confused certain aspects of the organization of the class Mollicutes.

Taxonomists once classified Mycoplasma and relatives in the phylum Firmicutes, consisting of low G+C Gram-positive bacteria such as Clostridium, Lactobacillus, and Streptococcus; but modern polyphasic analyses situate them in the phylum Tenericutes.

By the 1990s, it had become readily apparent that this approach was problematic: the type species, M. mycoides, along with other significant mycoplasma species like M. capricolum, is evolutionarily more closely related to the genus Spiroplasma in the order Entomoplasmatales than to the other members of the genus Mycoplasma. As a result, if the group was to be rearranged to match phylogeny, a number of medically important species (e.g. M. pneumoniae, M. genitalium) would have to be put in a different genus, causing widespread confusion in medical and agricultural communities. The genus was discussed multiple times by the International Committee on Systematic Bacteriology's (ICSB) subcommittee on Mollicutes between 1992 and 2011, to no effect.

Regardless of taxonomy, by 2007 it was solidly known that Molicutes could be divided into four nontaxonomic lineages.

• An "Acholeplasma" group consisting of Acholeplasmatales. This group is non-problematic, as it contains no species classified in what was then "Mycoplasma".
• A "Spiroplasma" or mycoides group containing M. mycoides and the aforementioned closely related species in "Spiroplasma" and Entomoplasmatales.
• A pneumoniae group containing M. pneumoniae and closely related species (M. muris, M. fastidiosum, U. urealyticum), the currently unculturable haemotrophic mollicutes, informally referred to as haemoplasmas (recently transferred from the genera Haemobartonella and Eperythrozoon), and Ureaplasma. This medically important group contains M. alvi (bovine), M. amphoriforme (human), M. gallisepticum (avian), M. genitalium (human), M. imitans (avian), M. pirum (uncertain/human), M. testudinis (tortoises), and M. pneumoniae (human). Most, if not all, of these species share some otherwise unique characteristics including an attachment organelle, homologs of the M. pneumoniae cytadherence-accessory proteins, and specialized modifications of the cell division apparatus.
• A hominis group containing M. hominis, M. bovis, and M. pulmonis among others.

As of 2018

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. 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) and National Center for Biotechnology Information (NCBI) now use the new nomenclature.

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".{{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

Gupta et al. 2019 performed some uncontroversial sorting of the order Mycoplasmatales.

Unassigned species

The GTDB and LTP phylogeny above does not include a number of names published under this genus that are either correct or pro-correct according to the LPSN. These species likely belong to a different genus under the standards of the 2018 reorganization, but has not been moved because a new combination has not been proposed, or because the new combination has not been made valid publication, or because the taxonomic opinion of the LPSN/LoRN refuses to use the new name as the correct name. The classification of LTP and GTDB is used here to assign a probable target genus.

Many new species have been proposed in Mycoplasma while disregarding the 2018 reorganization; see LPSN for a list. These will be included here and sorted by lineage eventually.

Hemotrophic mycoplasmas: This category includes species that should be moved to Eperythrozoon under the Gupta reorganization.

• "Ca. M. aoti" Barker et al. 2011
• "Ca. M. erythrocervae" Watanabe et al. 2010
• "Ca. M. haematobrackenitadaridae" Becker et al. 2025
• "Ca. M. haematocervi" corrig. Watanabe et al. 2010
• "Ca. M. haematodidelphidis" corrig. Messick et al. 2002
• "Ca. M. haematohominis" corrig. Millán et al. 2015
• "Ca. M. haematohydrochoeri" corrig. Vieira et al. 2021
• "Ca. M. haematomacacae" corrig. Maggi et al. 2013
• "Ca. M. haematominiopteri" corrig. Millán et al. 2015
• "Ca. M. haematomolossi" Becker et al. 2025
• "M. haematomyotis" Volokhov et al. 2023
• "Ca. M. haematonasuae" corrig. Collere et al. 2021
• "Ca. M. haematoparvum" Sykes et al. 2005
• "M. haematophyllostomi" Volokhov et al. 2023
• "Ca. M. haematoselmanitadaridae" Becker et al. 2025
• "Ca. M. haematosphigguri" corrig. Valente et al. 2021
• "Ca. M. haematotapirus" Mongruel et al. 2022
• "Ca. M. haematoterrestris" Mongruel et al. 2022
• "Ca. M. haematotraderitadaridae" Becker et al. 2025
• "Ca. M. haematovis" corrig. Hornok et al. 2009
• "Ca. M. haemobovis" Meli et al. 2010
• "Ca. M. haemomeles" Harasawa, Orusa & Giangaspero 2014
• "Ca. M. haemomuris" (Mayer 1921) Neimark et al. 2002
• "Ca. M. haemoparvum" Kenny et al. 2004
• "Ca. M. hemominiopterus" Millán et al. 2015

Nested in Mycoplasmoides:

• "M. bradburyae" Ramírez et al. 2023 – in GTDB

Nested in Mycoplasmopsis:

• M. hafezii Ziegler et al. 2019 – in LTP, close to Mycoplsmopsis alligatoris
• M. phocimorsus Skafte-Holm et al. 2023 – in LTP, close to "Mycoplasmopsis elephantis"

Synonimized before 2018 reorganization:

• "M. incognitus" Lo et al. 1989 → M. fermentans

Not in LTP/GTDB, some of which have a 16S in GenBank that can be used to assign the genus:

• "Ca. M. corallicola" Neulinger et al. 2009 – Mycoplsmopsis (among species mentioned in Gupta et al. (2018), "Mycoplsmopsis iguanae" was the highest 16S BLAST hit)
• "Ca. M. coregoni" corrig. Rasmussen et al. 2021
• "Ca. M. didelphidis" corrig. Pontarolo et al. 2021
• "M. insons" May et al. 2007
• "Ca. M. kahanei" Neimark et al. 2002
• "M. monodon" Ghadersohi & Owens 1998
• "M. pneumophila" Lyerova et al. 2008
• "Ca. M. ravipulmonis" Neimark, Mitchelmore & Leach 1998
• "Ca. M. salmoniarum" corrig. Rasmussen et al. 2021
• "M. sphenisci" Frasca et al. 2005
• "M. timone" Greub & Raoult 2001
• "Ca. M. tructae" Sanchez et al. 2020
• "Ca. M. turicense" corrig. Willi et al. 2006
• "M. volis" Dillehay et al. 1995
• "M. vulturii" Oaks et al. 2004

Synthetic mycoplasma genome

A chemically synthesized genome of a mycoplasmal cell based entirely on synthetic DNA which can self-replicate has been referred to as Mycoplasma laboratorium. It is therefore a model for a minimal genome, that is, a genome that is reduced to mostly essential genes.

References

References

1. (2004). "Sherris Medical Microbiology". McGraw Hill.
2. (2010). "Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look". Infectious Diseases in Obstetrics and Gynecology.
3. (1889). "Ueber der Pilzsymbiose der Leguminosen". Berichte der Deutschen Botanischen Gesellschaft.
4. (January 1973). "Etymology of the Term Mycoplasma". Int. J. Syst. Evol. Microbiol..
5. (2014). "Mollicutes Molecular Biology and Pathogenesis". Caister Academic Press.
6. (February 1956). "The classification and nomenclature of organisms of the pleuropneumonia group". J. Gen. Microbiol..
7. (2010). "Highlights of mycoplasma research—An historical perspective". Biologicals.
8. (1 October 2013). "Infection with Hemotropic Mycoplasma Species in Patients with or without Extensive Arthropod or Animal Contact". Journal of Clinical Microbiology.
9. (2016). "Dietary nitrogen alters codon bias and genome composition in parasitic microorganisms". Genome Biology.
10. "Mycoplasma".
11. (1954). "Untersuchungen über die Morphologie und die Vermehrung der pleuropneumonie-ähnlichen Organismen und der L-Phase der Bakterien. I. Lichtmikroskopische Untersuchungen". Archiv für Mikrobiologie.
12. (2014). "Clinical Microbiology made ridiculously simple". MedMaster, Inc..
13. (1954). "Untersuchungen über die Morphologie und die Vermehrung der pleuropneumonie-ähnlichen Organismen und der L-Phase der Bakterien. II. Elektronenmikroskopische Untersuchungen". Archiv für Mikrobiologie.
14. (1980). "Phylogenetic analysis of the mycoplasmas". Proceedings of the National Academy of Sciences of the United States of America.
15. (1990). "The microbe of pleuropneumonia. 1896". Rev. Infect. Dis..
16. Hayflick L, [[Robert M. Chanock. (June 1965). "Mycoplasma Species of Man". Bacteriol Rev.
17. (October 1995). "The minimal gene complement of Mycoplasma genitalium". Science.
18. (November 1996). "Complete sequence analysis of the genome of the bacterium Mycoplasma pneumoniae". Nucleic Acids Res..
19. (2002). "Molecular biology and pathogenicity of mycoplasmas". Kluwer Academic/Plenum.
20. (November 2000). "Towards a two-dimensional proteome map of Mycoplasma pneumoniae". Electrophoresis.
21. (2002). "Molecular Biology and Pathogenicity of Mycoplasmas (Razin S, Herrmann R, eds.)". Kluwer Academic/Plenum.
22. Brown DR. (2011). "Bergey's Manual of Systematic Bacteriology, Second Edition, Vol. 4, (Krieg NR, Staley JT, Brown DR, et al., eds.)". Springer.
23. (September 2007). "Phylogenetic relationships among mycoplasmas based on the whole genomic information". J. Mol. Evol..
24. (2018). "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". Antonie van Leeuwenhoek.
25. A.C. Parte. "Mycoplasma". [[List of Prokaryotic names with Standing in Nomenclature]] (LPSN).
26. Sayers. "Mycoplasma". [[National Center for Biotechnology Information]] (NCBI) taxonomy database.
27. (1 February 2020). "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)". International Journal of Systematic and Evolutionary Microbiology.
28. "Genus: Mycoplasmoides".
29. (10 August 2022). "Judicial Opinions 112–122". International Journal of Systematic and Evolutionary Microbiology.
30. (April 2019). "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". Antonie van Leeuwenhoek.
31. "The LTP".
32. "LTP_all tree in newick format".
33. "LTP_10_2024 Release Notes".
34. "GTDB release 09-RS220".
35. "bac120_r220.sp_labels".
36. "Taxon History".
37. [https://lpsn.dsmz.de/genus/mycoplasma LPSN lpsn.dsmz.de]
38. (July 2010). "Creation of a bacterial cell controlled by a chemically synthesized genome". Science.