Mycoplasma

Mycoplasmosis
Classification and external resources
ICD-10	A49.3
ICD-9	041.81

Mycoplasma is a genus of bacteria that lack a cell wall around their cell membrane.^[1] 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,^[2] can survive without oxygen and are typically about 0.1  µm in diameter.

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.^[3] 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.^[4]

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).^[5]

Species

Species that infect humans

Other species of Mycoplasma have been recovered from humans but are assumed to have been contracted from animals. The following use humans as the primary host:

History of mycoplasma research

Historically, lack of information on the pathogenic properties of Mycoplasma has been due to the lack of expertise of microbiology laboratories with culturing methods and inexperience. This has lead to difficulties in the detection of the bacteria in disease and high prevalence in persons with no symptoms of bacterial infection.^[6]

Characteristics

Over 100 species have been included in the genus Mycoplasma. Mollicutes are parasites or commensals of humans, animals, and plants. the genus Mycoplasma utilize to vertebrate hosts.

Cell morphology

First isolation

Taxonomy

Laboratory contaminant

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. 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).^[7] About 1% of published Gene Expression Omnibus data may have been compromised.^[8][9] Several antibiotic based formulation of anti-mycoplasma reagents have been developed over the years.^[10]

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.^[11]

Pathogenicity

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.^[12] 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.^[13]:293

Sexually transmitted infections

Mycoplasma and Ureaplasma species are not part of the normal vaginal flora. Some Mycoplasma species are spread through sexual contact.^[14]

Infertility

Some mycoplasmas have a negative effect on fertility.^[14]

Infant mortality

Low birth weight, pre-term infants are susceptible to mycoplasma infections.^[6]

Links to cancer

Several species of mycoplasma are frequently detected in different types of cancer cells.^[15][16][17] These species are:

• M. fermentans ^{[15][16][17][18][19][20]}
• M. genitalium ^[21]
• M. hyorhinis ^[15][21][22]
• M. penetrans ^{[15][16][17][18][20]}

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

Mycoplasma infection and host cell transformation

The presence of mycoplasma was first reported in samples of cancer tissue in the 1960s.^[17] 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.^[16] 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.^[16] 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.^[17]

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,^[18] and vav.^[16] 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.^[17] Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes.^[16] Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma.^[23] 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.^[18] 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.^[17] If the bacteria are killed using antibiotics ^[17] (i.e. ciprofloxacin ^[16] or Clarithromycin ^[24]) 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. ^[21][21]

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.^[25]

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.^[26]

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.^[27]

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.^[28]

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.^[24]

See also

• International Organization for Mycoplasmology (IOM)
• Sexually transmitted disease
• Vaginal flora
• Vaginal infection
• Vaginal disease
• Vaginal health

References

External links

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