|Gene map of Mycoplasma genitalium. Circularly arranged coloured bands are the genes (525 in number) in their position in the DNA. The genome has 580,070 nucleotide base pairs (580 kb).|
Tully et al., 1983
Mycoplasma genitalium is a small parasitic bacterium that lives on the ciliated epithelial cells of the urinary and genital tracts in humans. Its existence was first reported in 1981, and was eventually identified as new species of Mycoplasma in 1983. It is a sexually transmitted pathogen which can cause significant morbidity in men and women, and is a co-factor in HIV transmission. Specifically, it causes urethritis (inflammation of the urinary tract) both in men and women, and also cervicitis (inflammation of cervix) and pelvic inflammation in women. Its complete genome sequence was published in 1995. Up until 2003, when a new species of Archaea Nanoarchaeum equitans had its genome sequenced, it was regarded as a cellular unit with the smallest genome. With the genome sequence of Candidatus Carsonella ruddii in 2006, it remains the third smallest genome-sized organism.
The synthetic genome of M. genitalium named Mycoplasma genitalium JCVI-1.0 (after the research centre, J. Craig Venter Institute, where it was synthesised) was produced in 2008, becoming the first organism with synthetic genome. In 2014, researchers at The Scripps Research Institute discovered a new protein called Protein M from M. genitalium.
Discovery and description
Mycoplasma genitalium was originally isolated in 1980 from urethral specimens of two male patients suffering from non-gonococcal urethritis in the genitourinary medicine (GUM) clinic at St Mary's Hospital, Paddington, London. It was reported in 1981 by a team led by Joseph G. Tully. Under electron microscopy, it appears as flask-shaped cell having a narrow terminal portion that is crucial for its attachment to the host cell surfaces. The bacterial cell is slightly elongated somewhat like a vase, and measures 0.7-0.7 μm in length, 0.3-0.4 μm at the broadest region, and 0.06-0.08 μm at the tip. The base is broad while the tip is stretched into a narrow neck, which terminates with a cap. The terminal region has a specialised region called nap, which is absent in other Mycoplasma. Serological tests indicated that the bacterium was not related to known species of Mycoplasma. The comparison of genome sequences with other urinogenital bacteria such as M. hominis and Ureaplasma parvum revealed that M. genitalium is significantly different, especially in the energy-generating pathways, although it shared a core genome of ~250 protein-encoding genes. Infection by M. genitalium seems fairly common, can be transmitted between partners during unprotected sexual intercourse, and can be treated with antibiotic.
On 6 February 2014, The Scripps Research Institute announced the discovery of a new protein named Protein M from M. genitalium. The protein was identified during investigations on the origin of multiple myeloma, a B-cell carcinoma. To understand the long-term Mycoplasma infection, it was found that antibodies from multiple myeloma patients' blood were recognised by M. genitalium. The antibody reactivity was due to a protein never known before, and is chemically responsive to all types of human and nonhuman antibodies available. The protein is about 50 kDa in size, and composed of 556 amino acids. Contrary to their initial hypothesis that the antibody reactions were in response to mass infection with the bacterium, they found that Protein M evolved simply to bind to any antibody it encounters. By this property the bacterium can effectively evade the immune system of the host.
The genome of M. genitalium consists of 525 genes in one circular DNA of 580,070 base pairs. Scott N. Peterson and his team at the University of North Carolina at Chapel Hill reported the first genetic map using pulsed-field gel electrophoresis in 1991. They performed an initial study of the genome using random sequencing in 1993, by which they found 100,993 nucleotides and 390 protein-coding genes. Collobrating with researchers at the Institute for Genomic Research, which included Craig Venter, they made the complete genome sequence in 1995 using shotgun sequencing. Only 470 predicted coding regions (out of 482 protein encoding genes) were identified, including genes required for DNA replication, transcription and translation, DNA repair, cellular transport, and energy metabolism. It was the second complete bacterial genome ever sequenced, after Haemophilus influenzae. In 2006 the team at the J. Craig Venter Institute reported that only 382 genes are essential for biological functions. The small genome of M. genitalium made it the organism of choice in The Minimal Genome Project, a study to find the smallest set of genetic material necessary to sustain life.
Symptoms of infection
Infection with M. genitalium generally produces severe clinical symptom, or a combination of symptoms; but sometimes can be asymptomatic. It causes inflammation in the urethra (urethritis) both in men and women, which is associated with mucopurulent discharge in the urinary tract, and burning while urinating. In women, it causes cervicitis and pelvic inflammatory diseases, including endometritis and salpingitis. It is also supected with tubal factor infertility. Polymerase chain reaction analyses indicated that it is a cause of acute non-gonococcal urethritis (NGU) and probably chronic NGU. Unlike other Mycoplasma, the infection is not associated with bacterial vaginosis. It is highly associated with the intensity of HIV infection. It is also suspected to play a role in the development of prostate and ovarian cancers and lymphomas.
The U.S. Centers for Disease Control and Prevention has one specific recommended regimen, with azithromycin and another specific recommended regimen with doxycycline. As alternative regimens, the agency has specific regimens each with erythromycin or erythromycin ethylsuccinate or ofloxacin or levofloxacin.
Studies have demonstrated that a 5 day course of azithromycin has a superior cure rate than a single dose. Further, a single dose of azithromycin can lead to the bacteria becoming resistant to azithromycin. Based on these findings, UK doctors are moving to a 5 day azithromycin regimen. Doxycycline is also still used but moxifloxacin is seen as an alternative treatment. Among Swedish patients, doxycycline is relatively ineffective (with a cure rate of 48% for women and 38% for men); and a five-day treatment with azithromycin is neither prescribed due to drug resistance.
On 6 October 2007, Craig Venter announced that a team of scientists led by Nobel laureate Hamilton Smith at the J. Craig Venter Institute had successfully constructed a synthetic DNA using which they planned to make the first synthetic genome. Reporting in The Guardian, Venter said that they have stitched together a DNA strand of 381 genes long and contained 580,000 base pairs, based on the genome of M. genitalium. On 24 January 2008 they announced the successful creation of a synthetic bacterium which they named Mycoplasma genitalium JCVI-1.0 (the name of the strain indicating J. Craig Venter Institute with its specimen number). They synthesised and assembled the complete 582,970-base pair genome of the bacterium. The final stages of synthesis involved cloning the DNA into the bacterium E. coli for nucleotide production and sequencing. This produced large fragments of approximately 144,000 base pairs or 1/4th of the whole genome. Finally, the products were cloned inside the yeast Saccharomyces cerevisiae to synthesize the 580,000 base pairs. The molecular size of the synthetic bacterium is 360,110 kilodaltons (kDa). Printed in 10 10-point font, the letters of the genome cover 147 pages.
On 20 July 2012, Stanford University and the J. Craig Venter Institute announced successful simulation of the complete life cycle of a Mycoplasma genitalium cell, in the journal Cell. The entire organism is modeled in terms of its molecular components, integrating all cellular processes into a single model. Using object oriented programming to model the interactions of 28 categories of molecules including DNA, RNA, proteins, and metabolites, and running on 128-core Linux cluster, the simulation takes 10 hours for a single M. genitalium cell to divide once — about the same time the actual cell takes — and generates half a gigabyte of data.
- Tully, J. G.; Taylor-Robinson, D.; Rose, D. L.; Cole, R. M.; Bove, J. M. (1983). "Mycoplasma genitalium, a New Species from the Human Urogenital Tract". International Journal of Systematic Bacteriology 33 (2): 387–396. doi:10.1099/00207713-33-2-387.
- Tully, Joseph G.; Cole, Roger M.; Taylor-Robinson, David; Rose, David L. (1981). "A newly discovered Mycoplasma in the human urinogenital tract". The Lancet 317 (8233): 1288–1291. doi:10.1016/S0140-6736(81)92461-2.
- Horner, Patrick; Blee, Karla; Adams, Elisabeth (2014). "Time to manage Mycoplasma genitalium as an STI". Current Opinion in Infectious Diseases 27 (1): 68–74. doi:10.1097/QCO.0000000000000030. PMID 24322592.
- Fraser, C. M.; Gocayne, J. D.; White, O.; Adams, M. D.; Clayton, R. A.; Fleischmann, R. D.; Bult, C. J.; Kerlavage, A. R.; Sutton, G.; Kelley, J. M.; Fritchman, J. L.; Weidman, J. F.; Small, K. V.; Sandusky, M.; Fuhrmann, J.; Nguyen, D.; Utterback, T. R.; Saudek, D. M.; Phillips, C. A.; Merrick, J. M.; Tomb, J.-F.; Dougherty, B. A.; Bott, K. F.; Hu, P.-C.; Lucier, T. S. (1995). "The Minimal Gene Complement of Mycoplasma genitalium". Science 270 (5235): 397–404. doi:10.1126/science.270.5235.397. PMID 7569993.
- Nakabachi, A.; Yamashita, A.; Toh, H.; Ishikawa, H.; Dunbar, H. E.; Moran, N. A.; Hattori, M. (2006). "The 160-Kilobase Genome of the Bacterial Endosymbiont Carsonella". Science 314 (5797): 267–267. doi:10.1126/science.1134196. PMID 17038615.
- "The Ultimate Decoy: Scripps Research Institute Scientists Find Protein that Helps Bacteria Misdirect Immune System". The Scripps Research Institute (TSRI). Retrieved 9 August 2014.
- Taylor-Robinson, D.; Horner, P. J. (2001). "The role of Mycoplasma genitalium in non-gonococcal urethritis". Sexually Transmitted Infections 77 (4): 229–231. doi:10.1136/sti.77.4.229. PMC 1744340. PMID 11463919.
- Daley, G.; Russell, D.; Tabrizi, S.; McBride, J. (2014). "Mycoplasma genitalium: a review". International Journal of STD & AIDS 25 (7): 475–487. doi:10.1177/0956462413515196. PMID 24517928.
- Taylor-Robinson, D (1995). "The Harrison Lecture. The history and role of Mycoplasma genitalium in sexually transmitted diseases". Genitourinary Medicine 71 (1): 1–8. doi:10.1136/sti.71.1.1. PMC 1195360. PMID 7750946.
- Blanchard, Alain; Bébéar, Cécile (2011). "The evolution of Mycoplasma genitalium". Annals of the New York Academy of Sciences 1230 (1): E61–E64. doi:10.1111/j.1749-6632.2011.06418.x. PMID 22417108.
- Grover, R. K.; Zhu, X.; Nieusma, T.; Jones, T.; Boero, I.; MacLeod, A. S.; Mark, A.; Niessen, S.; Kim, H. J.; Kong, L.; Assad-Garcia, N.; Kwon, K.; Chesi, M.; Smider, V. V.; Salomon, D. R.; Jelinek, D. F.; Kyle, R. A.; Pyles, R. B.; Glass, J. I.; Ward, A. B.; Wilson, I. A.; Lerner, R. A. (2014). "A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union". Science 343 (6171): 656–661. doi:10.1126/science.1246135. PMC 3987992. PMID 24503852.
- "The ultimate decoy: Protein helps bacteria misdirect immune system". ScienceDaily. 6 February 2014. Retrieved 9 August 2014.
- "Birth of the digital bacteria". New Scientist 215 (2875): 19. 2012-07-28. doi:10.1016/s0262-4079(12)61932-0.
- Peterson, Scott N.; Schramm, Nara; Hu, Ping-chuan; Bott, Kenneth F.; Hutchison, Clyde A. (1991). "A random sequencing approach for placing markers on the physical map of". Nucleic Acids Research 19 (21): 6027–6031. doi:10.1093/nar/19.21.6027. PMC 329062. PMID 1945886.
- Peterson, SN; Hu, PC; Bott, KF; Hutchison CA, 3rd (1993). "A survey of the Mycoplasma genitalium genome by using random sequencing". Journal of Bacteriology 175 (24): 7918–7930. PMC 206970. PMID 8253680.
- Glass, J. I.; Assad-Garcia, N.; Alperovich, N.; Yooseph, S.; Lewis, M. R.; Maruf, M.; Hutchison, C. A.; Smith, H. O.; Venter, J. C. (2006). "Essential genes of a minimal bacterium". Proceedings of the National Academy of Sciences 103 (2): 425–430. doi:10.1073/pnas.0510013103. PMC 1324956. PMID 16407165.
- Razin, S (1997). "The minimal cellular genome of mycoplasma". Indian Journal of Biochemistry & Biophysics 34 (1–2): 124–30. PMID 9343940.
- Manhart, Lisa E. (2013). "Mycoplasma genitalium: An emergent sexually transmitted disease?". Infectious Disease Clinics of North America 27 (4): 779–792. doi:10.1016/j.idc.2013.08.003. PMID 24275270.
- Taylor-Robinson, D. (2002). "Mycoplasma genitalium - an up-date". International Journal of STD & AIDS 13 (3): 145–151. doi:10.1258/0956462021924776. PMID 11860689.
- Weinstein, Scott A; Stiles, Bradley G (2013). "Recent perspectives in the diagnosis and evidence-based treatment of". Expert Review of Anti-infective Therapy 10 (4): 487–499. doi:10.1586/eri.12.20. PMID 22512757.
- Zarei, O; Rezania, S; Mousavi, A (2013). "Mycoplasma genitalium and cancer: a brief review.". Asian Pacific Journal of Cancer Prevention 14 (6): 3425–8. doi:10.7314/apjcp.2013.14.6.3425. PMID 23886122.
- Diseases Characterized by Urethritis and Cervicitis
- Yew, H. S.; Anderson, T.; Coughlan, E.; Werno, A. (2011). "Induced macrolide resistance in Mycoplasma genitalium isolates from patients with recurrent nongonococcal urethritis". Journal of Clinical Microbiology 49 (4): 1695–1696. doi:10.1128/JCM.02475-10. PMC 3122813. PMID 21346049.
- Mycoplasma Genitalium Treatment Choices
- Anagrius, Carin; Loré, Britta; Jensen, Jørgen Skov; Coenye, Tom (2013). "Treatment of Mycoplasma genitalium. Observations from a Swedish STD Clinic". PLoS ONE 8 (4): e61481. doi:10.1371/journal.pone.0061481. PMC 3620223. PMID 23593483.
- Pilkington, Ed (6 October 2007). "I am creating artificial life, declares US gene pioneer". The Guardian (Guardian News and Media Limited). Retrieved 9 August 2014.
- Kowalski, Heather. "Venter Institute Scientists Create First Synthetic Bacterial Genome". J. Craig Venter Institute. Retrieved 9 August 2014.
- Gibson, D. G.; Benders, G. A.; Andrews-Pfannkoch, C.; Denisova, E. A.; Baden-Tillson, H.; Zaveri, J.; Stockwell, T. B.; Brownley, A.; Thomas, D. W.; Algire, M. A.; Merryman, C.; Young, L.; Noskov, V. N.; Glass, J. I.; Venter, J. C.; Hutchison, C. A.; Smith, H. O. (2008). "Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome". Science 319 (5867): 1215–1220. doi:10.1126/science.1151721. PMID 18218864.
- Ball, Philip (2008-01-24). "Genome stitched together by hand". Nature News. doi:10.1038/news.2008.522.
- "Scientists Create First Synthetic Bacterial Genome -- Largest Chemically Defined Structure Synthesized In The Lab". ScieceDaily. 24 January 2008. Retrieved 9 August 2014.
- Karr, Jonathan R.; Sanghvi, Jayodita C.; Macklin, Derek N.; Gutschow, Miriam V.; Jacobs, Jared M.; Bolival, Benjamin; Assad-Garcia, Nacyra; Glass, John I.; Covert, Markus W. (2010). "A Whole-Cell Computational Model Predicts Phenotype from Genotype". Cell 150 (2): 389–401. doi:10.1016/j.cell.2012.05.044. PMC 3413483. PMID 22817898.
- "In First, Software Emulates Lifespan of Entire Organism". The New York Times. 20 July 2012. Retrieved 2012-07-20.
- Mycoplasma genitalium Reference Work at the UK Health Protection Agency
- Mycoplasma genitalium G-37 genome page