Mollicutes is a class of bacteria distinguished by the absence of a cell wall and its peptidoglycan. The word Mollicutes is derived from Latin 'soft, pliable' and '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, 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.
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.
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.Shmuel Razin, David Yogev and Yehudith Naot Molecular Biology and Pathogenicity of Mycoplasmas. Micr. and Molec. Biology Reviews, December 1998, pp. 1094–1156, Vol. 62, No. 4
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. In 1954, this mode of proliferation has been shown by continual observations of live cells using phase-contrast microscopy.
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.
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.
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.pdf In 1967 the class Mollicutes, containing the order Mycoplasmatales, was proposed by the Subcommittee on Taxonomy of the Mycoplasmata. 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).Revised minimal standards for description of new species of the class Mollicutes (division Tenericutes) PDF ; Daniel R. Brown, Robert F. Whitcomb and Janet M. Bradbury (2007) Int J Syst Evol Microbiol 57 2703–2719;
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 (see Figure).
Three divisions of the bacteria
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) 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 "Firmicutes"), and the "Mollicutes", without a cell wall.N.E. Gibbons & R.G.E. Murray Proposals Concerning the Higher Taxa of Bacteria Int J Syst Bacteriol Vol. 28 (1) Jan. 1978, pp. 1–6.
The phylum for Mollicutes
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.C.R. Woese, J. Maniloff and L.B. Zablen Phylogenetic analysis of the mycoplasmas Proc. Natl. Acad. Sci. USA Vol. 77, No. 1, pp. 494–498, January 1980 The results of molecular phylogenetic analyses have been partly dependent on the chosen molecular marker, like rRNA, elongation factor or another protein.Ludwig, W. and Schleifer, K.H. Molecular phylogeny of bacteria based on comparative sequence analysis of conserved genes Microbial phylogeny and evolution, 2005, p. 70–98. Phylogenetic trees based on phosphoglycerate kinase (Pgk) amino acid sequences' indicated a monophyletic origin for the Mollicutes within the Bacillota. DOI 10.1099/ijs.0.02868-0
An early edition of Bergey's Manual of Systematic Bacteriology placed class Mollicutes within phylum Bacillota,Taxonomic Outline of the Prokaryotes. Bergey's Manual of Systematic Bacteriology. Garrity, Bell & Lilburn; Second Edition, Release 5.0 (2004); pp. 140–204. .K. Johansson and B. Pettersson, Taxonomy of Mollicutes books.google.com (2002) whereas in the announced 2nd edition, they are moved to a separate phylum Tenericutes (later renamed Mycoplasmatota).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. ; PDF Validation of the Publication of New Names and New Combinations ... Int. J. Syst. Bacteriol.; July 1984, pp. 355–357 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". In the Taxonomic Outline of Bacteria and Archaea (TOBA Release 7.7), March 2007, the Mollicutes are a class in the phylum Bacillota.Garrity, et al. The Taxonomic Outline of Bacteria and Archaea (TOBA Release 7.7); March 2007.
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).
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.
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". Gupta and Oren wrote a rebuttal in 2020, further detailing the pre-existing taxonomic problems.; see also LPSN FAQ on correct name 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 (and for the purpose of the LPSN, they remain the "correct names"). However, the older names also remain valid; their use remains acceptable under the Code.
Gupta et al. 2019 performed some uncontroversial sorting of the order Mycoplasmatales.
Phylogeny The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnology Information (NCBI).
16S rRNA based LTP_10_2024 120 marker proteins based GTDB 10-RS226 ♦ Mollicutes