Difference between revisions of "Mycoplasma genitalium"
|Line 1:||Line 1:|
Latest revision as of 15:44, 1 July 2011
A Microbial Biorealm page on the genus Mycoplasma genitalium
Higher order taxa
Bacteria; Firmicutes; Mollicutes; Mycoplasmatales; Mycoplasmataceae; Mycoplasma
Description and significance
Mycoplasma genitalium is a parasitic bacterium with the smallest known genome of any free living bacteria at 580,070 bp long. They are believed to have evolved from gram-positive bacteria through a process of degenerative evolution, leading to the loss of many ancestral genes and the reduction of its genome.
"M. genitalium is so far one out fifteen mycoplasma species of human origin." They are often found invading and adhering to the epithelial linings of the urogenital tracts, but they have also been discovered in the respiratory tract. M. genitalium is associated with many urogenital tract infections, in both men and women. In fact M. genitalium was first found in two men with non-gonococcal urethritis.
Besides its importance as a pathogen, its genome has been extensively studied in order to determine the minimal set of genes essential for life.
In 1995, the entire genome of M. genitalium was sequenced in less than 6 months using the random shotgun sequencing technique. It was found to have the smallest known genome of any free-living organism at about 580 kilobase pairs long, with 479 coding sequences for proteins. For comparison M. pneumoniae has 677 protein coding sequences, H. influenzae has 1703, and E. coli K-12 has 4,288.
The genome-sequencing projects have shown that there is a 62% similarity between the coding regions of Bacillus subtilis and a 56% similarity to E. coli. There is even closer similarity to the Gram-positive species of Lactobacillus and Clostridium. This provides strong evidence that the mycoplasmas are more closely related to Gram-positive bacteria.
Low GC content is a characteristic of all mycoplasmas. M. genitalium possess an average GC content of 32%. Genes coding for rRNA average 44% and 52% for tRNA. The GC content for rRNA and tRNA are much higher than the rest of the genome due to the importance of their secondary structures.
The Mycoplasmas evolved through a process of degenerate evolution from Gram-positive bacteria. They have lost many genes such as those involved with cell wall synthesis and various biosynthetic pathways, as they adapted to a more parasitic lifestyle. This allows them to have some of the smallest genomes of any bacterial organism. In addition, their UGA codon is used as another codon for tryptophan instead of a stop codon found in other organisms.
M. genitalium lack any genes for amino acid biosynthesis and contain few genes for nucleic acid, vitamins, and fatty acid biosynthesis. They must acquire these components from their host or through an artificial medium. This makes them difficult to study in the lab under in vitro conditions, due to their strict growth requirements. They also lack genes for oxidative metabolism (Kreb cycle, or Entner-Doudoroff pathway), gluconeogenesis, catalase and peroxidase, or other toxic oxygen protective enzymes. They also appear to possess few regulatory proteins, such as two-component systems and no identifiable transcription factors. They do however possess the genes necessary for DNA replication, transcription, and translation, but even these contain a minimal set of rRNA and tRNA genes. They also contain genes for glycolysis, phospholipids metabolism, and for converting vitamins to cofactors. They have less DNA repair genes compared to E. coli and H. influenzae. It is assumed however that the genes detected such as uracil DNA glycosylase, exinuclease ABC genes, and recA must be essential for proper DNA repair in all organisms.
While M. genitalium have been able to reduce its genome during the course of its evolution as a parasite, it must maintain genes necessary for this mode of life. A significant portion of its genome is devoted to the transport of nutrients from its host such as glucose and fructose, as well as genes for attachment organelles, adhesins, and antigenic variation to evade the host immune system. In fact it’s estimated that 5% of its total DNA is devoted to repeat fragments used for antigenic recombination of adhesin proteins.
Due to its minimal set of genes needed for protein synthesis and DNA replication, protein synthesis and cell replication occur much slower compared to E. coli. M. genitalium grow much more slowly with a generation time of about 24 hours.
Cell Structure and Metabolism
M. genitalium is flask shaped and do not have a cell wall like all mycoplasma species. Lacking a cell wall they have only a plasma membrane, with over two thirds of its mass containing proteins. Virtually all mycoplasma lipids such as phospholipids, glycolipids, and neutral lipids, are located in the cell membrane. Membrane lipoproteins are also present and strongly antigenic, and undergo size variations.
They lack genes for synthesizing any fatty acid. Most mycoplasmas generally synthesize their own membrane phospholipids and glycolipids from the fatty acids provided from their host. There is a price for this gene saving. Being unable to regulate membrane fluidity by controlling their fatty acid biosynthesis, the mycoplasmas overcome this by incorporating large amounts of cholesterol from their host into their membrane. Cholesterol serves as a an effective buffer of membrane fluidity.
M. genitalium is a motile mycoplasma. It uses a specialized tip structure to attach to surfaces and glide across them. The average speed is about 0.1 μ/s, which is slower than that recorded for M. pneumoniae. This tip structure also serves as the attachment organelle, allowing M. genitalium to adhere to eukaryotic cells. Attachment is mediated mostly by the adhesin protein MgPa, which undergoes antigenic recombination.
As mentioned earlier, M. genitalium is deficient in many genes coding for components of many biosynthetic pathways, including energy metabolism. M. genitalium depend mostly on glycolysis for the production of ATP, which is less efficient than oxidative phosphorylation. Genes that encode the components of the pyruvate dehydrogenase complex, phosphotransacetylase, and acetate kinase were also detected, as well as an incomplete pentose phosphate pathway. Many energy-producing systems are lacking such as the TCA (tricarboxylic acid) cycle, and no quinones and cytochromes were found in any of the mycoplasmas. Despite these limited ATP producing systems, M. genitalium grow well in vivo due to the relatively small amounts of ATP needed for their limited biosynthetic pathways.
Due to the scarcity of genes involved in biosynthetic pathways, mycoplasmas depend on a supply of nutrients from their hosts and exist as parasites of various animals and plants. M. genitalium is found primarily in the urogenital tract of humans; however they have been isolated in the respiratory tract as well.
Lacking a cell wall and possessing only a plasma membrane, M. genitalium is much more osmotically sensitive than other bacteria. As a parasite in the human urogenital tract they can exist in an osmotically constant environment. Its transmission by sexual contact also ensures minimal exposure to the external environment.
"Mycoplasmas are benign pathogens causing mostly mild and chronic infections, but rarely killing their hosts." It is possible that mycoplasmas, including M. genitalium are evolving towards symbiosis.
The urogenital tract appears to be the primary tissue infected by M. genitalium, however they have also been isolated in the respiratory tract. Tissue damage is only partially caused by toxins and harmful metabolites produced by M. genitalium, such as hydrogen peroxide and super-oxide metabolites. Most likely the much of the damage is caused by the inflammatory response of the host immune system.
In men, M. genitalium is a major agent in urogenital tract disease. In a range of studies they have been found in 10-45% of men with non-gonococcal urethritis. The role of M. genitalium in women is less understood, but they are believed to be able to cause cervicitis and pelvic inflammatory disease (PID). Only incomplete evidence has been established for the role of M. genitalium on infertility, while its role in bacterial vaginosis (BV) and adverse pregnancy in women have not been fully determined. M. genitalium can be sexually transmitted with rates similar to Chlamydia trachomatis, another pathogen which can cause urethritis.
Adhesion of mycoplasmas to host cells is required for colonization and for infection. Without adhesion there can be no infection. They attach to host cells using a specialized tip structure that contain proteins called adhesins. The main adhesin protein is encoded by the MgPa gene, followed by a gene encoding a 114 kDa protein of unknown function. Multiple repeat fragments of both these genes are found throughout the genome and make up 4.7% of its total genome, a high cost considering its limited genome. Recombination of the MgPa operon with the repeat fragments may generate almost unlimited variation, allowing for the evasion of the host’s immune response and “to adapt to various cell surfaces.” Other variable antigens are currently under study and may prove to offer additional variation for M. genitalium, including the lipoproteins on the plasma membrane.
There is also evidence that M. genitalium can enter host cells using their tip structure. Being able to exist as an intracellular pathogen may allow for protection against the host’s immune system and it could also explain the difficulties in fully eliminating the disease, despite antibiotic treatments.
The macrolide antibiotic group appears to be the most effective form of treatment of M. genitalium. Further research is still being done on proper treatment.
Most past research on Mycoplasma genitalium has focused on its minimal genome in order to determine the genes necessary for life. Experiments done in the Institute of Genomics Research on Mycoplasma genitalium, tried to determine the genes that are essential for a living organism. By comparing Mycoplasma genitalium genome with Mycoplasma pneumonia and utilizing gene knockout techniques, scientists discovered that only 300 out of 517 genes were necessary for life. The functions of 111 of these genes in M. genitalium were unknown. It was found that genes for some tRNAs that were thought as essential, were not necessary. The genes that are defined as essential in their work only apply under laboratory conditions and not in the natural environment. Their work also has a lot of ethical and environmental implications as it could pave the way for the “creation of a living organism in the laboratory.”
Studies have also been done on the association of mycoplasmas and AIDS, specifically their role in AIDS activation. Their ability as possible factors in AIDS activation has increased research into mycoplasma and their pathogenesis. “The substantial number of studies carried out on the AIDS-associated mycoplasmas, M. fermentans and M. penetrans, have considerably advanced our knowledge of mycoplasma cell biology and host immune system modulation…however, thus far the proposed role of mycoplasmas in AIDS activation remains controversial and doubtful.”
While the role of Mycoplasma genitalium in causing non-gonococcal urethritis in men is well known, more recent research has focused on its pathology in women. While its role in causing cervicitis has been known, it has only recently been linked to pelvic inflammatory disease in women. Its role in other urogenital tract infections in women is still being studied, as well as M. genitalium effects on fertility and pregnancy.
1. C.M. Fraser et al. Science. 1995. Volume 270: 397-403
2. Deborah, Josefson. “Scientists try to discover how many genes are necessary to build a living organism.” BMJ (British Medical Journal). December 18, 1999. Volume 319(7225): 1592.
3. Jensen, Jorgen Skov. “Mycoplasma genitalium infections” Danish Medical Bulletin – No. 1. February 2006. Volume 53: 1-27.
4. Jensen, Jorgen Skov. “Mycoplasma genitalium: the aeticological agent of urethritis and other sexually transmitted diseases.” Journal of the European Academy of Dermatology and Venereology. January 2004. Volume 18(1): 1-11.
5. Maniloff, Jack. “The minimal cell genome: ‘On being the right size.’” Proceedings of the National Academy of Sciences of the United States of America. September 1996. Volume 93: 10004-10006.
6. Morgan, Nacy A. “Microbial Minimalism: Genome Reduction in Bacterial Pathogens.” Cell. March 8, 2002. Volume 108: 583-586.
7. Peterson, Scott et al. “Characterization of repetitive DNA in the Mycoplasma genitalium genome: Possible role in the generation of antigenic variation.” Proceedings of the National Academy of Sciences of the United States of America. December 1995. Volume 92: 11829-11833.
8. Peterson, Scott and Claire M. Fraser. “The complexity of simplicity.” Genome Biology. 2001. Volume 2(2).
9. Razin, Shmuel. “The minimal cellular genome of mycoplasma.” Indian Journal of Biochemistry & Biophysics. Feb-Apr 1997. Volume 34(1-2):124-30.
10. Razin, S., Yogev, D., and Naot, Y. “Molecular Biology and Pathogenicity of Mycoplasmas.” Microbiology Molecular Biology Review. December 1998. Volume 62(4): 1094–1156.
11. Walsh, Nancy. “M. genitalium tied to pelvic inflammatory disease: sexual transmission – Gynecology.” OB/GYN News. Sept 15, 2003.
Edited by Michael Yam, student of Rachel Larsen and Kit Pogliano