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 (1998). They are believed to be simplest form of independent life with the minimal set of genes. M. genitalium is so far one out fifteen mycoplasma species of human origin. They are often found adhering to the epithelial linings of the urogenital tracts and are associated with many urogenital infections, in both men and women. In fact M. genitalium was first isolated in two men with non-gonococcal urethritis. M. genitalium have also been found in the respiratory tract.
Besides its importance as a pathogen, its genome has been extensively studied and used in comparison with other small genome organisms, 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 1740, 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, however 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 with low GC contents.
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 for these functional RNAs.
The Mycoplasmas evolved through a process of degenerate evolution from gram-positive bacteria. They have lost many genes involved in cell wall synthesis and biosynthetic systems as they adapted to a more parasitic lifestyle, as a result they have some of the smallest genomes of any self-replicating 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 most these products from their host or through an artificial medium. This makes them difficult to study under classical experimental methods due to their strict growth requirements. They also lack genes for oxidative metabolism (Kreb cycle, or Entner-Doudoroff pathway), gluconeogenesis, catalase, 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 can be assumed however that the genes detected such as uracil DNA glycosylase, exinuclease ABC genes, and recA must be essential for proper DNA repair.
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 parasitism. A significant portion of its genome is devoted to the transport of exogenous nutrients 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 cell pole adhesins.
M. genitalium possess the minimum set of genes needed for protein synthesis and DNA replication, however as a result of this, protein synthesis and cell replication occurs much slower compared to E. coli. M. genitalium grow slowly with a generation time of 24 hours.
E. coli and M. genitalium both have 12% of their genome occupied by intergenic non-coding regions such as control elements, promoters, and terminators. However, M, genitalium possess more operon systems, probably reducing the number of regulatory elements for the transcription of genes and further contributing to the reduction of its genome. This increases gene density with the average gene size for M. genitalium at 1,040 base pairs, compared with 900 in H. influenzae.
Cell Structure and Metabolism
M. genitalium have a flask-like shape and they 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 and the rest being membrane lipids. Virtually all mycoplasma lipids are located in the cell membrane such as phospholipids, glycolipids, and neutral lipids. Membrane lipoproteins are also found to be much higher in mycoplasma species compared to other eubacteria membranes. In addition their membrane lipoproteins are strongly antigenic, many of which undergo antigenic and/or size variations.
They lack genes for synthesizing any fatty acid and therefore depend on their host for their supply. Most mycoplasmas generally synthesize their own membrane phospholipids and glycolipids from the exogenously provided fatty acids. There is a price for this gene saving. Being deficient in the ability to regulate membrane fluidity by controlling their fatty acid biosynthesis, the mycoplasmas overcome this difficulty by incorporating large quantities of cholesterol from their hosts into their membrane. Cholesterol serves as a very 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. Genes that encode the components of the pyruvate dehydrogenase complex, phosphotransacetylase, and acetate kinase were also detected, as well as a deficient pentose phosphate pathway. Many energy-producing systems are lacking such as the tricarboxylic acid cycle, and no quinones and cytochromes were found in any of the mycoplasmas. ATP is produced in mycoplasmas by subtrate-level phosphorylation, less efficient than oxidative phosphorylation. Despite these limited and inefficient ATP producing systems, M. genitalium grow well in vivo most likely due to the relatively small investment 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 as such they 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 limited only by their plasma membrane, M. genitalium is much more osmotically sensitive than walled bacteria. As a parasite in the human urogenital tract they can exist in an osmotically constant environment. Its transmission by sexual contact also ensures its minimal exposure to the external environment.
Mycoplasmas are benign pathogens, causing mostly mild and chromic infections and rarely killing their hosts. It is possible that mycoplasmas, including M. genitalium are evolving towards symbiosis.
How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
Application to Biotechnology
Does this organism produce any useful compounds or enzymes? What are they and how are they used?
Enter summaries of the most recent research here--at least three required
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.
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.
Morgan, Nacy A. “Microbial Minimalism: Genome Reduction in Bacterial Pathogens.” Cell. March 8, 2002. Volume 108: 583-586.
Peterson, Scott et al. “Characterization of repetitive DNA in the Mycoplasma genitalium genome: Possible role in the generation go antigenic variation.” Proceedings of the National Academy of Sciences of the United States of America. December 1995. Volume 92: 11829-11833.
Razin, Shmuel. “The minimal cellular genome of mycoplasma.” Indian Journal of Biochemistry & Biophysics. 1997 Feb-Apr 1997. Volume 34(1-2):124-30.
Walsh, Nancy. “M. genitalium tied to pelvic inflammatory disease: sexual transmission – Gynecology.” OB/GYN News. Sept 15, 2003.
Edited by student of Michael Yam