| Mycoplasma genitalium | |
|---|---|
| Other names: Mycoplasmoides genitalium | |
_model_of_a_Mycoplasma_genitalium_cell.jpg) | |
| 3D wholecell model of a Mycoplasma genitalium . It does not include the terminal attachmentorganelle. | |
 | |
| Specialty | Infectious disease |
| Symptoms | Burning with urination, penial or vaginal discharge, enlarged groin lymph nodes,pelvic inflammation[1] |
| Complications | Infertility,ectopic pregnancy,preterm birth[1] |
| Causes | Vaginal or anal sex with someone who is infected[2] |
| Risk factors | High number of sexual partners[1] |
| Diagnostic method | PCR testing[1] |
| Prevention | Condoms, having one or no sexual partners[2] |
| Treatment | Doxycycline,azithromycin,moxifloxacin[1] |
| Frequency | 1.3 to 3.9% (reproductive age)[1] |
Mycoplasma genitalium (MG,Mgen) is asexually transmitted infection of theurinary andgenital tracts.[1][3] Often there may be no symptoms; however, when present they may includeurethritis (burning with urination, discharge, enlarged groin lymph nodes),cervicitis (abnormal smell, discharge), orpelvic inflammation.[1] Complications may includeinfertility,ectopic pregnancy, andpreterm birth.[1] It also increases the risk ofHIV.[1]
It is spread by vaginal or anal sex, with someone who is infected.[2] It is due to a very smallbacterium of size 0.58Mbp, with475 genes.[4] Risk factors include a larger number of sexual partners.[1] Testing is recommended in those with persistent symptoms not due to other causes.[1] Testing people without symptoms is discouraged.[1] Diagnosis is byPCR testing of a vaginal swab in women or a urethral swab or urine specimen in men.[1] It does not generally affect the mouth.[1]
Resistance toantibiotics is common, particularlyazithromycin and less oftenmoxifloxacin.[1] Typical treatment involvesdoxycycline 100 mg BID for 7 days followed by either azithromycin for another 4 days or moxifloxacin for another 7 days depending on resistance testing.[1] Testing and treatment of sexual partners may also be carried out.[1][5] When azithromycin resistant disease is present in pregnancy,pristinamycin may be used or treatment may be delayed until after delivery.[1]
Mycoplasma genitalium affects about 1.3% of people of reproductive age inhigh income countries and 3.9% of people inlow and middle income countries.[1] Males and females are affected with similar frequency.[1] Rates are higher infemale sex workers and the less educated.[1] The bacteria was first isolated in 1980,[6] and was identified as a new species ofMycoplasma in 1983.[7]
Infection can beasymptomatic. Or can causeinflammation in theurethra (urethritis) both in men and women, which is associated withmucopurulent discharge in theurinary tract, andburning while urinating. In women, it causescervicitis andpelvic inflammatory disease (PID), includingendometritis andsalpingitis.[8] Women may also have bleeding after sex ortubal factor infertility.[9][10][11] For men, the most common signs are painful urination or a watery discharge from the penis.[12]Polymerase chain reaction indicated that it is a cause of acutenon-gonococcal urethritis (NGU) and probably chronic NGU. It is strongly associated with persistent and recurring non-gonococcal urethritis (NGU) responsible for 15 percent to 20 percent ofsymptomatic NGU cases in men.[13] Unlike otherMycoplasma, the infection is not associated withbacterial vaginosis.[14] It is highly associated with the intensity of HIV infection.[15] It is unclear if Mgen could play a role in the development ofprostate andovarian cancers andlymphomas.[16]
| Mycoplasma genitalium | |
|---|---|
 | |
| Gene map ofMycoplasma genitalium. Circularly arranged coloured bands are the genes (525 in number) in their position in the DNA. The genome has 580,070base pairs (580 kb). | |
Scientific classification | |
| Domain: | Bacteria |
| Kingdom: | Bacillati |
| Phylum: | Mycoplasmatota |
| Class: | Mollicutes |
| Order: | Mycoplasmatales |
| Family: | Mycoplasmataceae |
| Genus: | Mycoplasma |
| Species: | M. genitalium |
| Binomial name | |
| Mycoplasma genitalium Tullyet al., 1983[7] | |
The genome ofM. genitalium consists of 525 genes[17] in one circular DNA of 580,070base pairs.[4] The first genetic map usingpulsed-field gel electrophoresis was reported in 1991.[18] They performed an initial study of the genome usingrandom sequencing in 1993, by which they found 100,993 nucleotides and 390 protein-coding genes.[19] They made the complete genome sequence in 1995 usingshotgun sequencing.[4] Only 470 predictedcoding regions (out of 482 protein encoding genes) were identified, includinggenes required forDNA replication,transcription andtranslation,DNA repair,cellular transport, andenergy metabolism. It was the second complete bacterial genome ever sequenced, afterHaemophilus influenzae. In 2006, it was reported that only 382 genes are essential for biological functions.[20] The small genome ofM. genitalium made it the organism of choice inThe Minimal Genome Project, a study to find the smallest set of genetic material necessary to sustainlife.[21]
There is a consistent association ofM. genitalium infection and female reproductive tract syndromes.M. genitalium infection was significantly associated with increased risk of preterm birth, spontaneous abortion, cervicitis, and pelvic inflammatory disease. In addition, this pathogen may latently infect thechorionic villi tissues of pregnant women, thereby impacting pregnancy outcome.[22] Infertility risk is also strongly associated with infection withM. genitalium, although evidence suggests it is not associated with male infertility.[23] WhenM. genitalium is a co-infectious agent risk associations are stronger and statistically significant.[24]M. genitalium is strongly associated with HIV-1.[9]
Recent research shows that prevalence of Mgen is currently higher than other commonly occurringsexually transmitted infections (STIs).[25] Mgen is a fastidious organism with prolonged growth durations. This makes detection of the pathogen in clinical specimens and subsequent isolation, extremely difficult.[26] Lacking acell wall,mycoplasma remains unaffected by commonly usedantibiotics.[27] The absence of specific serological assays leavesnucleic acid amplification tests (NAAT) as the only viable option for detection of MgenDNA orRNA.[28] However, samples with positive NAAT for the pathogen should be tested formacrolide resistancemutations, which are strongly correlated toazithromycin treatment failures, owing to rapid rates of mutation of the pathogen.[29] Mutations in the23S rRNA gene of Mgen have been linked with clinical treatment failure and high levelin vitro macrolide resistance.[30] Macrolide resistance mediating mutations have been observed in 20-50% of cases in the UK, Denmark, Sweden, Australia, and Japan.[29] Resistance is also developing towards the second-lineantimicrobials likefluoroquinolone.[31]
According to the European guidelines, the indication for commencement of diagnosis for Mgen infection are:[28]
Screening for Mgen with a combination of detection and macrolide resistance mutations will provide the adequate information required to develop personalised antimicrobial treatments, in order to optimise patient management and control the spread ofantimicrobial resistance (AMR).[28][32]
Owing to the widespreadmacrolide resistance, samples that are positive for Mgen should ideally be followed up with an assay capable of detecting mutations that mediate antimicrobial resistance. The European Guideline on Mgen infections, in 2016,[33] recommended complementing the molecular detection of Mgen with an assay capable of detecting macrolide resistance-associated mutations.[citation needed]
The U.S.Centers for Disease Control and Prevention recommends a step-wise treatment withdoxycycline for 7 days followed immediately by a 7-day course ofmoxifloxacin as the preferred therapy.[34][35] If resistance assay testing is available, and the Mgen is sensitive to macrolides, the CDC recommends a 7-day course of doxycycline followed by a 4-day course ofazithromycin. If moxifloxacin is not available; the CDC recommends as an alternative regiment: 7 days of doxycycline followed by the 4-day course of azithromycin, with a test of cure 21 days after treatment being required due to the high rate of macrolide resistance. The CDC notes thatbeta lactam antibiotic are not effective against Mgen as the organism lacks a cell wall.[35]
Treatment is becoming increasingly difficult due to rapidly growingantimicrobial resistance.[36] Diagnosis and treatment is further hampered by the fact thatMycoplasma genitalium infections are not routinely tested.[37] Studies have demonstrated that a 5-day course of azithromycin has a superior cure rate compared to a single, larger dose. Further, a single dose of azithromycin can lead to the bacteria becoming resistant to azithromycin.[38] Among Swedish patients, doxycycline was shown to be relatively ineffective (with a cure rate of 48% for women and 38% for men); and treatment with a single dose of azithromycin is not prescribed due to it inducing antimicrobial resistance. The five-day treatment with azithromycin showed no development of antimicrobial resistance.[39] Based on these findings, UK doctors are moving to the 5-day azithromycin regimen. Doxycycline is also still used, andmoxifloxacin is used as a second-line treatment in case doxycyline and azithromycin are not able to eradicate the infection.[40][41]In patients where doxycycline, azithromycin and moxifloxacin all failed,pristinamycin has been shown to still be able to eradicate the infection.[40]
Mycoplasma genitalium was originally isolated in 1980 fromurethralspecimens of two male patients withnon-gonococcal urethritis in the genitourinary medicine (GUM) clinic atSt Mary's Hospital, Paddington, London.[42][43] It was reported in 1981 by a team led by Joseph G. Tully.[44] Under electron microscopy, it appears as a flask-shaped cell with a narrow terminal portion that is crucial for its attachment to the host cell surfaces.[45] The bacterial cell is slightly elongated somewhat like a vase, and measures 0.6–0.7 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 otherMycoplasma.Serological tests indicated that the bacterium was not related to known species ofMycoplasma. The comparison of genome sequences with other urinogenital bacteria, such asM. hominis andUreaplasma parvum, revealed thatM. genitalium is significantly different, especially in theenergy-generating pathways, although it shared a core genome of ~250 protein-encoding genes.[46]
The discovery ofProtein M, a new protein fromM. genitalium, was announced in February 2014.[47] The protein was identified during investigations on the origin ofmultiple myeloma, a B-cell hematologic neoplasm. To understand the long-termMycoplasma infection, it was found thatantibodies from multiple myeloma patients' blood were recognised byM. 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.[48]
In 2007, there was successful constructedsynthetic DNA to make the first synthetic genome. They had stitched together a DNA strand containing 381 genes, consisting of 580,000 base pairs, based on the genome ofM. genitalium.[49] On 24 January 2008, they announced the successful creation of a synthetic bacterium, which they namedMycoplasma genitalium JCVI-1.0 (the name of the strain indicating J. Craig Venter Institute with its specimen number).[50] 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 bacteriumE. 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 yeastSaccharomyces cerevisiae to synthesize the 580,000 base pairs.[51][52] The molecular size of the synthetic bacterial genome is 360,110kilodaltons (kDa). Printed in 10-point font, the letters of the genome cover 147 pages.[53]
In 2012, there was successful simulation of the complete life cycle of aMycoplasma genitalium cell.[54] 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 a 128 computer Linux cluster, the simulation takes 10 hours for a singleM. genitalium cell to divide once—about the same time the actual cell takes—and generates half a gigabyte of data.[55]
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