Mycoplasma genitalium (also known as MG, Mgen, or since 2018, Mycoplasmoides genitalium) is a sexually transmitted, small pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in humans. Medical journals in 2007 and 2015 reported that Mgen is becoming more common. Resistance to multiple antibiotics, including the macrolide azithromycin, until recently the most reliable treatment, is becoming prevalent. The bacterium was first isolated from the urogenital tract of humans in 1981 and was identified as a new species of Mycoplasma in 1983. It increases the risk of HIV spread in men and women, with higher occurrences in those previously treated with azithromycin antibiotics.

Mgen is a bacterium recognized for causing urethritis in both men and women along with cervicitis and pelvic inflammation in women. It presents clinically similar symptoms to that of Chlamydia trachomatis infection and has shown higher incidence rates, compared to both Chlamydia trachomatis and Neisseria gonorrhoeae infections in some populations.

Infection with Mgen can be symptomatic or asymptomatic. Both men and women may experience inflammation in the urethra (urethritis), characterized by mucopurulent discharge in the urinary tract, and burning while urinating. In women, it causes cervicitis and pelvic inflammatory diseases (PID), including endometritis and salpingitis. Women may also experience bleeding after sex and it is also linked with tubal factor infertility. For men, the most common signs are painful urination or a watery discharge from the penis.

There is a consistent association of M. 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 the chorionic villi tissues of pregnant women, thereby impacting pregnancy outcome. Infertility risk is also strongly associated with infection with M. genitalium, although evidence suggests it is not associated with male infertility. When M. genitalium is a co-infectious agent risk associations are stronger and statistically significant.

Polymerase chain reaction analyses indicated that it is a cause of acute non-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 of symptomatic NGU cases in men. Unlike other mycoplasmas, the infection is not associated with bacterial vaginosis. It is highly associated with the intensity of HIV infection. Some scientists are performing research to determine if Mgen could play a role in the development of prostate and ovarian cancers and lymphomas in some individuals. These studies have yet to find conclusive evidence to suggest a link.

The genome of M. genitalium strain G37^T consists in one circular DNA molecule 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 sequencing in 1993, by which they found 100,993 nucleotides and 390 protein-coding genes. Collaborating with researchers at The Institute for Genomic Research (TIGR; now the J. Craig Venter Institute), which included Craig Venter, they completed the genome sequence in 1995 using shotgun sequencing. Only 470 predicted coding regions were identified in 1995, 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. Later data from KEGG reports 476 protein-coding genes and 43 RNA genes, totaling 519. It is unclear where the "525" gene count for the G37^T stems from and what gene calling procedure was used. The current genome annotation in the Uniprot reference proteome lists 483 proteins.

In the original genome sequence, 374 of the 470 predicted proteins had at least a "putative" function assigned. 96 genes had no matches to any known proteins in other organisms. In 2025, 30 years after the genome was published, 26 proteins are still annotated (in Uniprot) as "probable" (e.g. rbgA/MG442 is probably the ribosome biogenesis GTPase A) and 28 proteins are annotated as "putative" (e.g. MG125 is a Putative phosphatase [EC 3.1.3.-]). Notably, 146 proteins remain annotated as "uncharacterized", with about a dozen having some predicted function. The function of more than 100 proteins thus appears to remain largely mysterious.

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.