|Classification and external resources|
Mycoplasma is a genus of bacteria that lack a cell wall around their cell membrane. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans, including M. pneumoniae, which is an important cause of atypical pneumonia and other respiratory disorders, and M. genitalium, which is believed to be involved in pelvic inflammatory diseases. Mycoplasma are the smallest bacterial cells yet discovered, can survive without oxygen and are typically about 0.1 µm in diameter. Hundreds of mycoplasmas infect animals.
- 1 Origin of the name
- 2 Species
- 3 Species that infect humans
- 4 Pathophysiology
- 5 Characteristics
- 6 Taxonomy
- 7 Laboratory contaminant
- 8 Synthetic mycoplasma genome
- 9 Pathogenicity
- 9.1 Sexually transmitted infections
- 9.2 Infertility
- 9.3 Infant mortality
- 9.4 Links to cancer
- 10 See also
- 11 References
- 12 External links
Origin of the name
The term mycoplasma, from the Greek μυκής, 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 genus name Mycoplasma for certain filamentous microorganisms imagined to have both cellular and acellular stages in their life cycles, which could explain how they were visible with a microscope but passed through filters impermeable to bacteria.
Later the name for Mycoplasma was pleuropneumonia-like organisms (PPLO), broadly referring to organisms similar in colonial morphology and filterability to the causative agent of contagious bovine pleuropneumonia (CBPP).
Species that infect humans
Other species of Mycoplasma other than those listed below have been recovered from humans but are assumed to have been contracted from animals. The following use humans as the primary host:
Micoplasma spp have been isolated from women with bacterial vaginosis. M. genitalium infection is associated with increased risk of cervicitis, pelvic inflammatory disease, preterm birth, and spontaneous abortion, and of infertility. There are associations of mycoplasmas with fetal respiratory distress syndrome, bronchopulmonary dysplasia, and intraventricular hemorrhage in preterm infants.
Mycoplasma species are often found in research laboratories as contaminants in cell culture. Mycoplasmal cell culture contamination occurs due to contamination from individuals or contaminated cell culture medium ingredients[clarification needed]. Mycoplasma cells are physically small – less than 1 µm – and they are therefore difficult to detect with a conventional microscope.
Mycoplasmas may induce cellular changes, including chromosome aberrations, changes in metabolism and cell growth. Severe Mycoplasma 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.
It has been estimated that at least 11 to 15% of U.S. laboratory cell cultures are contaminated with mycoplasma. A Corning study showed that half of U.S. scientists did not test for mycoplasma 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 page 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for mycoplasma, 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). About 1% of published Gene Expression Omnibus data may have been compromised. Several antibiotic based formulation of anti-mycoplasma reagents have been developed over the years.
Synthetic mycoplasma genome
The P1 antigen is the primary virulence factor of mycobacteria. 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. Several Mycoplasma species can cause disease, including M. pneumoniae, which is an important cause of atypical pneumonia (formerly known as "walking pneumonia"), and M. genitalium, which has been associated with pelvic inflammatory diseases. Mycoplasma infections in humans are associated with skin eruptions in 17% of cases.:293
Sexually transmitted infections
Some mycoplasmas have a negative effect on fertility.
Low birth weight, pre-term infants are susceptible to mycoplasma infections.
Links to cancer
- M. fermentans 
- M. genitalium 
- M. hyorhinis 
- M. penetrans 
Mycoplasma infection and host cell transformation
The presence of mycoplasma was first reported in samples of cancer tissue in the 1960s. Since then there have been several studies trying to find and prove the connection between mycoplasma and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic. 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 a solid support in order to grow and proliferate as well as the normal contact dependent inhibition cells.
Possible intracellular mechanisms of mycoplasmal malignant transformation
Karyotypic changes related to mycoplasma infections
Cells infected with mycoplasma 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. Proto-oncogenes with increased activity caused by these genetic abnormalities include those encoding c-myc, HRAS, and vav. 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 mycoplasma as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known.
- Partial reversibility of malignant transformations
The malignant transformation induced by mycoplasma 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 that reversibility is possible varies greatly; it depends primarily on the mycoplasma involved. In the case of M. fermentans, the transformation is reversible up until around week 11 of infection and starts to become irreversible between week 11 and 18. If the bacteria are killed using antibiotics  (i.e. ciprofloxacin  or Clarithromycin ) 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. Mycoplasma genitalium and Mycoplasma hyorhinis induce malignant phenotype in benign human prostate cells (BPH-1) that were "non-tumorigenic" after 19 weeks of exposure. 
Types of cancer associated with mycoplasma
Colon cancer: In a study to understand the effects of mycoplasma contamination on the quality of cultured human colon cancer cells, it was found that there is a positive correlation between the amount of M. hyorhinis present in the sample and the percentage of CD133 positive cells (a glycoprotein with an unknown function). Further tests and analysis are required to determine the exact reason for this phenomenon.
Gastric cancer: There are strong indications that the infection of M. hyorhinis contributes to the development of cancer within the stomach and increases the likelihood of malignant cancer cell development.
Lung cancer: Studies on lung cancer have supported the belief that there is more than a coincidental positive correlation between the appearance of Mycoplasma strains in patients and the infection with tumorigenesis. Because this is a such a new area of research, more studies must be performed to further understand the correlation and determine possible preventative steps for lung cancer involving mycoplasma.
Prostate cancer: p37, a protein encoded for by M. hyorhinis, has been found to promote the invasiveness of prostate cancer cells. The protein also causes the growth, morphology, and the gene expression of the cells to change, causing them to become a more aggressive phenotype.
Renal Cancer: Patients with renal cell carcinoma (RCC) exhibited a significantly high amount of Mycoplasma sp. compared with the healthy control group. This suggests that mycoplasma may play a role in the development of RCC.
- International Organization for Mycoplasmology (IOM)
- Sexually transmitted disease
- Vaginal flora
- Vaginal infection
- Vaginal disease
- Vaginal health
- Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp. 409–12. ISBN 0-8385-8529-9.
- Richard L. Sweet, Ronald S. Gibbs. Infectious Diseases of the Female Genital Tract. Lippincott Williams & Wilkins, 2009.
- Larsen, Bryan; Hwang, Joseph (2010). "Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look". Infectious Diseases in Obstetrics and Gynecology 2010: 1–7. doi:10.1155/2010/521921. ISSN 1064-7449.
- Krass CJ, Gardner MW (January 1973). "Etymology of the Term Mycoplasma" (PDF). Int. J. Of Syst. Bact. 23 (1): 62–64. doi:10.1099/00207713-23-1-62.
- Browning GF, Citti C (editors) (2014). Mollicutes Molecular Biology and Pathogenesis (1st ed.). Caister Academic Press. pp. 1–14. ISBN 978-1-908230-30-0.
- Edward DG, Freundt EA (February 1956). "The classification and nomenclature of organisms of the pleuropneumonia group" (PDF). J. Gen. Microbiol. 14 (1): 197–207. doi:10.1099/00221287-14-1-197. PMID 13306904.
- Waites, K. B.; Katz, B.; Schelonka, R. L. (2005). "Mycoplasmas and Ureaplasmas as Neonatal Pathogens". Clinical Microbiology Reviews 18 (4): 757–789. doi:10.1128/CMR.18.4.757-789.2005. ISSN 0893-8512.
- Lis, R.; Rowhani-Rahbar, A.; Manhart, L. E. (2015). "Mycoplasma genitalium Infection and Female Reproductive Tract Disease: A Meta-Analysis". Clinical Infectious Diseases. doi:10.1093/cid/civ312. ISSN 1058-4838.
- John Ryan (2008). "Understanding and Managing Cell Culture Contamination" (PDF). Corning Incorporated. p. 24.
- Aldecoa-Otalora E, Langdon W, Cunningham P, Arno MJ (December 2009). "Unexpected presence of mycoplasma probes on human microarrays". BioTechniques 47 (6): 1013–5. doi:10.2144/000113271. PMID 20047202.
- Link into RNAnet showing contamination of GEO. Press plot and drag blue crosshairs to expose links to description of experiments on human RNA samples)
- BM-Cyclin by Roche, MRA by ICN, Plasmocin by Invivogen and more recently De-Plasma by TOKU-E.
- Gibson DG, Glass JI, Lartigue C, Noskov VN, Chuang RY, Algire MA, Benders GA, Montague MG, Ma L, Moodie MM, Merryman C, Vashee S, Krishnakumar R, Assad-Garcia N, Andrews-Pfannkoch C, Denisova EA, Young L, Qi ZQ, Segall-Shapiro TH, Calvey CH, Parmar PP, Hutchison CA, Smith HO, Venter JC (July 2010). "Creation of a bacterial cell controlled by a chemically synthesized genome". Science 329 (5987): 52–6. doi:10.1126/science.1190719. PMID 20488990.
- Parija, Subhash Chandra (2014). Textbook of Microbiology & Immunology. Elsevier Health Sciences. ISBN 9788131236246.
- James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- Ljubin-Sternak, Suncanica; Mestrovic, Tomislav (2014). "Review: Clamydia trachonmatis and Genital Mycoplasmias: Pathogens with an Impact on Human Reproductive Health". Journal of Pathogens 2014 (183167). doi:10.1155/204/183167.
- Huang S, Li JY, Wu J, Meng L, Shou CC (April 2001). "Mycoplasma infections and different human carcinomas". World Journal of Gastroenterology 7 (2): 266–269. PMID 11819772.
- Sinkovics JG (February 2012). "Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)". International Journal of Oncology 40 (2): 305–349. doi:10.3892/ijo.2011.1248. PMID 22076306.
- Tsai S, Wear DJ, Shih JW, Lo SC (October 1995). "Mycoplasmas and oncogenesis: Persistent infection and multistage malignant transformation". Proceedings of the National Academy of Sciences of the United States of America 92 (22): 10197–10201. doi:10.1073/pnas.92.22.10197. PMID 7479753.
- Cimolai N (August 2001). "Do mycoplasmas cause human cancer?". Canadian Journal of Microbiology 47 (8): 691–697. doi:10.1139/w01-053. PMID 11575494.
- Jiang S, Zhang S, Langenfeld J, Lo SC, Rogers MB (May 2008). "Mycoplasma infection transforms normal lung cells and induces bone morphogenetic protein 2 expression by post-transcriptional mechanisms". Journal of Cellular Biochemistry 104 (2): 580–594. doi:10.1002/jcb.21647. PMID 18059017.
- Zhang S, Tsai S, Lo SC (May 2006). "Alteration of gene expression profiles during mycoplasma-induced malignant cell transformation". BMC Cancer 6: 116. doi:10.1186/1471-2407-6-116. PMID 16674811.
- Namiki K, Goodison S, Porvasnik S, Allan RW, Iczkowski KA, Urbanek C, Reyes L, Sakamoto N, Rosser CJ (September 2009). "Persistent exposure to mycoplasma induces malignant transformation of human prostate cells". PLoS ONE 4 (9): 1–9. doi:10.1371/journal.pone.0006872. PMC 2730529. PMID 19721714.
- Chan PJ, Seraj IM, Kalugdan TH, King A (November 1996). "Prevalence of mycoplasma conserved DNA in malignant ovarian cancer detected using sensitive PCR–ELISA". Gynecologic Oncology 63 (2): 258–260. doi:10.1006/gyno.1996.0316. PMID 8910637.
- Hu X, Yu J, Zhou X, Li Z, Xia Y, Luo Z, Wu Y (Jan 2014). "A small GTPase-like protein fragment of Mycoplasma promotes tumor cell migration and proliferation in vitro via interaction with Rac1 and Stat3.". J Mol Med Rep 9 (1): 173–179. doi:10.3892/mmr.2013.1766. PMID 24172987.
- Pehlivan M, Pehlivan S, Onay H, Koyuncuoglu M, Kirkali Z (February 2005). "Can mycoplasma-mediated oncogenesis be responsible for formation of conventional renal cell carcinoma?". Urology 65 (2): 411–414. doi:10.1016/j.urology.2004.10.015. PMID 15708077.
- Mariotti E, Gemei M, Mirabelli P, D'Alessio F, Di Noto R, Fortunato G, Del Vecchio L (March 2010). "The percentage of CD133+ cells in human colorectal cancer cell lines is influenced by Mycoplasma hyorhinis infection". BMC Cancer 10: 120–125. doi:10.1186/1471-2407-10-120. PMID 20353562.
- Yang H, Qu L, Ma H, Chen L, Liu W, Liu C, Meng L, Wu J, Shou C (November 2010). "Mycoplasma hyorhinis infection in gastric carcinoma and its effects on the malignant phenotypes of gastric cancer cells". BMC Gastroenterology 10: 132–140. doi:10.1186/1471-230X-10-132. PMID 21062494.
- Apostolou P, Tsantsaridou A, Papasotiriou I, Toloudi M, Chatziioannou M, Giamouzis G (October 2011). "Bacterial and fungal microflora in surgically removed lung cancer samples". Journal of Cardiothoracic Surgery 6: 137. doi:10.1186/1749-8090-6-137. PMID 21999143.
- Urbanek C, Goodison S, Chang M, Porvasnik S, Sakamoto N, Li CZ, Boehlein SK, Rosser CJ (June 2011). "Detection of antibodies directed at M. hyorhinis p37 in the serum of men with newly diagnosed prostate cancer". BMC Cancer 11 (1): 233–238. doi:10.1186/1471-2407-11-233. PMID 21663671.
- Compare the size of these small bacteria to the sizes of other cells and viruses.
- MedPix(r)Images Mycoplasma Pneumonia
- Ureaplasma Infection: eMedicine Infectious Diseases
- Antibiotics formulation for eradication of mycoplasma in cell culture media
- Mycoplasma elimination and prevention in cell culture