Mycoplasma pneumoniae is a member of the class Mollicutes, meaning soft skin. Along with the other members of this class (Acholeplasma, Anaeroplasma, Asteroleplasma, Spiroplasma, and Ureaplasma) Mycoplasma are characterized by their unusually small genome as well as their complete lack of a bacterial cell wall. M. pneumoniae was first linked to respiratory infections in 1898 when Roux and Nocard isolated the organisms from bovine pleuropneumonia specimens. M. pneumoniae is currently thought to be responsible for both tracheobronchitis and primary atypical pneumonia, however, much of the research regarding this bacterium is conflicting. Even though M. pneumoniae has one of the smallest known genomes, there is still much to be learned about this mystery bug.
Fun Fact #1: Unlike bacteria who use UGA as the universal stop codon, M. pneumoniae recognizes UGA as a mitochondria would, for tryptophan.
When Mycoplasma species were first cultured, they were thought to have been viruses because of their size. After correctly ascertaining the presence of both DNA and RNA, they were deemed bacteria. These microorganisms are so tiny, they are able to fit through 450-nm pore diameter membrane filters. Proportionate to their size, mycoplasma species are know to have genomes ranging in size from 600Kb to 2300Kb and have a coding capacity of about 700 proteins. Mycoplasma pneumoniae has a genome of 800Kb which has been mapped by researchers in Germany in Richard Herrmann's laboratory .
Click here for enhanced EcoRI map or here for the complete genome of M. pneumoniae.
These tiny bacteria developed over time by degenerate evolution from gram-postive bacteria that average genome sizes of 2500-2700Kb. Some of the ancestors of mycoplasma include Lactobacillus, Bacillus, Streptococcus and 2 Chlostridium species. Despite the significant loss of genetic material, Mycoplasma are able to survive through a parasitic lifestyle. They have never been found growing freely as living organisms because they depend on their host for such things as fatty acids, amino acids, precursors for nucleic acid synthesis and cholesterol. The ability of M. pneumoniae to reproduce with its miniscule genome makes it an obvious choice for a model system for defining the minimal requirements for an autonomously replicating cell.
Fun Fact #2: The proteome (total proteins expressed by a genome) is being fully sequenced for M. pneumoniae by B. Uberle, J. Regula in cooperation with A. Gorg, TU Munchen, and R. Frank, ZMBH, Heidelberg.
Mycoplasma pneumoniae lacks a cell wall which leads to osmotic instability. To create some structural support, M. pneumoniae utilizes sterols, much like eukaryotic cells, in its triple-layered membrane (fig. 17-83 from Atlas, Ronald M. Principles of Microbiology, 2nd Edition. Wm.C.Brown Publishers, Dubuqe, IA. 1997. pg. 1046). The bacterium may be able to survive without a cell wall because it lives in an osmotically stable environment, the animal (human) host, as well as its protein network which resembles an ancestral cytoskeleton. The combination of these unique characteristics creates a different scenario for treatment of a mycoplasmal infection than other bacteria. The lack of a cell wall prevents the utilization of a B-lactam antibiotic, such as penicillin and cycloserine, because they act specifically to disrupt the cell wall. The use of cholesterol in M. pneumoniae, however, allows for a different avenue for antibiotic therapies usually ineffective on bacteria, such as the use of polyenes.
The absence of a cell wall is likely to facilitate a bacterium to host interaction through which compounds can be exchanged. This transfer can include not only the nutrients and supplementary amino acids, etc. that is necessary for the support of bacterial growth, but also toxic metabolic compounds. It is thought that this bacterial surface parasitism causes severe damage to the host cell, however, not one toxin has been identified as the culprit.
The morphology of mycoplasma colonies is often likened to a "fried-egg" because they form a dense central core, which penetrates downward into the agar, surrounded by a circular spreading area that is lighter in color.
Many of the pathogenic mycoplasma species express specialized tip organelles used to make direct contact with eukaryotic cells. These organelles are paramount in the virulence associated with M. pneumoniae. This figure can be found on MedScape.
Fun Fact #3: The smallest mycoplasma units that are able to grow independently are coccoid elements between 0.2 and 0.3 µm in size.
Mycoplasma pneumoniae can be communicated through close personal contact via respiratory droplets. Some researchers have noticed a prevalence of infections occurring in the Fall and Winter. While this theory is not widely recognized to be true, there is much evidence to suggest that pneumonia caused by a M. pneumoniae infection cycles through populations every 4 to 5 years. The life cycle of M. pneumoniae can follow two paths. It reproduces either through binary fission or cell elongation follwed by multiple cell divisions to form coccoid cells.
Recent research has found a receptor on the surface of M. pneumoniae thought to be integral in the attachment to the host cell surface. This receptor can attach to a number of different cell types such as respiratory tract epithelia and red blood cells. At high concentrations, M. pneumoniae can inhibit ciliary action within the respiratory tract as well as cause cell necrosis. This damage is caused by cytotoxins from M. pneumoniae as well as indirectly from the host immune response.
Atlas, Ronald M. Principles of Microbiology, 2nd Edition. Wm.C.Brown Publishers, Dubuqe, IA. 1997. pg. 1046
Fun Fact #4: There are 5 recently proposed (and controversial) associations between mycoplasma infections and human disease: AIDS, Malignant Transformation, Gulf War Syndrome, Crohn's Disease, and Rheumatoid Arthritis and Other Human Arthritides for more information see Medscape.
Interestingly enough, the most effective way that humans have for fighting off a mycoplasma infection is through our own immune response, specifically the complement system. As mentioned above, B-lactam antibiotics are ineffective for obvious reasons. Without a cell wall, B-lactams like penicillin, are rendered useless because they act specifically on the cell wall. Though polyene antibiotics can be used against the cholesterols found in the membrane of mycoplasma, they can also act against the plasma membrane of the host cells.
The complement system mentioned above is actually a cascade of proteins normally found in the tissue or the blood of an animal host that participates in antigen-antibody reactions that eventually lead to cell lysis. There are different pathways through which complement is initiated, but each ends with the same effect, death of the bacteria via a membrane attack complex (MAC). The Classical Pathway of complement begins by the association of antibodies to the bacteria whereas the Alternative Pathway is initiated by bacterial surface molecules binding to host molecules. These are the two main pathways through which complement is initiated.
MAC ATTACK: The membrane attack complex can kill the bacteria through 4 different mechanisms.
There is not much information regarding how to prevent a mycoplasma infection other than the common sense aspect of washing your hands frequently and avoiding close contact with patients known to be infected.
Fun Fact #5: One theory on why it is so difficult to treat mycoplasma infections is that the bacteria might be capable of fusing its own sterol-containing membrane with the host cell plasma membrane, in effect, disguising itself!
Not all human hosts colonized by M. pneumoniae actually develop pneumonia, however, the virulence attributed to this bacteria is correlated to the lipid-associated membrane proteins that are exposed on the cell surface. The expression of specialized polar tip organelles for mediating attachment to host cells is a coordinate interaction between desgnated adhesins, interactive proteins, and adherence-accessory proteins. By concentrating adhesins at the tip of this structure, mycoplasma are able to colonize mucous membranes and eukaryotic cell surfaces (please see MedScape for figure reference). Some research points toward certain mycoplasma species being commensal to healthy people. Currently there are great deficits in our knowledge of mycoplasma virulence and pathogenesis.
Mycoplasma pneumoniae is also thought to be involved in mediating other diseases and infections in its monopolization of the immune response. Some patients have developed severe bacterial and viral infections just after or during a M. pneumoniae infection. This is thought to occur by the creation of an environment that is anatomically, physiologically, and/or immunologically conducive to other organisms for invasion as well as for cellular damage.
Fun Fact #6: The M. pneumoniae adhesin sequences bear significant homology to mammalian structural proteins (ie.CD4 and Major Histocompatiblity Complex type II lymphocyte proteins). It is thought that this homology is what provokes an "antiself response" that leads to immune disorders.
M. pneumoniae possesses only one full-length copy of the adhesin genes in a single operon, but has available to its defenses, multiple copies of very similar adhesins. These copies can be utilized through homologous recombination to evade the host immune response. Research has shown that pathogenic mycoplasma choreograph the rearrangement of DNA using the multiple copies of adhesin gene sequences to supercede the natural disadvantages to having a small genome. This "gene shuffling" also allows for a high rate of reinfection of patients. M. pneumoniae does not have to evade the host immune response, necessarily, because it is able to create an "antiself" response. By serving as B-cell and T-cell mitogens, mycoplasmas could be able to activate antiself T cells or polyclonal B cells.
Mycoplasma are also known to be a major annoyance in laboratory research because of its innate ability to contaminate just about everything.
There are a number of symptoms that are associated with a M. pneumoniae infection, some more rare than others.
There are also many objective findings that help to determine precisely, and not-so-precisely, whether a pneumonia is caused by M. pneumoniae or a different source.
1. Cold agglutinins (non-specific, erythrocyte-agglutinating antibodies) were used in many early research endeavors. The problem with cold agglutinins were two-fold. Only half of the humans infected with M. pneumoniae actually produce cold agglutinins. Not to mention that false-positive titers can occur with lymphoproliferative disorders, infectious mononucleosis, syphilis, influenza, adenovirus infection, and Legionella pneumophila infection.
2. The replacement test for the cold agglutinin titer is the complement fixation test which detcts both IgG and IgM specific to M. pneumoniae. A four-fold rise in complement fixation titer during the acute and convalescent phases is indicative of a M. pneumoniae infection. Unfortunately, there is a problem with this test as well. It takes 10-14 days for M. pneumoniae to grow to the appropriate stage for the complement fixation titer to work.
3. A third test has recently been found that utilizes an enzyme immunoassay for M. pneumoniae specific IgM. This IgM is found in 80% of M. pneumoniae cases within 1 week of infection. Again, the down fall of this test is that the IgM levels are found to be elevated up to 4 years after infection.
4. Complete blood cell counts can also be used, though white cell counts exceed 10,000/µL in only 30% of the cases.
5. Erythrocyte sedimentation rates are used to determine M. pneumoniae infections.
6. Chest radiographs of patients suffering from M. pneumoniae pneumonia often show unilateral segmental pneumonia. Three lobes are rarely involved.
Fun Fact #7: A similar bacteria-mediated immune response disorder to those linked to M. pneumoniae is the onset of acute rheumatic fever after streptococcal infection.
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This web site was created by Katherine J. Howard on February 22, 1999. All of the information on this page was gleaned from the above web sites and other cited reference books. If you have any questions regarding figures, please feel free to contact me at khoward@panther.middlebury.edu. Thanks, and I hope you enjoy learning about Mycoplasma pneumoniae.