The Unique Microbiology and Molecular Pathogenesis of Mycoplasma genitalium

Abstract

Mycoplasma genitalium is increasingly appreciated as a common cause of sexually transmitted disease syndromes, including urethritis in men and cervicitis, endometritis, pelvic inflammatory disease, and possibly preterm birth, tubal factor infertility, and ectopic pregnancy in women. Despite these disease associations, which parallel those of Chlamydia trachomatis and Neisseria gonorrhoeae, the mechanisms by which this pathogen elicits inflammation, causes cellular damage, and persists in its only natural host (humans) are unique and are not fully understood. The purpose of this review is to briefly provide a historical background on the discovery, microbiology, and recognition of M. genitalium as a pathogen, and then summarize the recent advances in our understanding of the molecular biology and pathogenesis of this unique urogenital organism. Collectively, the basic scientific discussions herein should provide a framework for understanding the clinical and epidemiological outcomes described in the accompanying articles in this supplemental issue.

Keywords: genitalium; immunity; mycoplasma; recombination; regulation.

Figure 1.

Mycoplasma genitalium structure and interactions with human reproductive tract epithelial cells. A, B, Curved terminal organelle (arrowhead in A) is a dominant feature of the cell body of M. genitalium in scanning electron micrographs [2] (A) and is covered with a “nap” containing the attachment proteins MgpB and MgpC, as observed by transmission electron microscopy [1] (B). Owing to substantial genetic, functional, and morphological homology, the complex structure of the terminal organelle is inferred to be similar to that of Mycoplasma pneumoniae. (C) M. pneumoniae terminal organelle structure, as seen with electron cryotomography [3]; letters indicate different component protein complexes identified in M. pneumoniae, which are presumed to correlate with homologous proteins in M. genitalium. (D–F) Interaction of M. genitalium with cultured human ectocervical epithelial cells. The terminal organelle of M. genitalium with its electron dense core is clearly visible in (D and E), (arrowheads) and is involved in attachment to host epithelial cells. The intimate interaction between M. genitalium and epithelial cells surface and M. genitalium is not limited to the terminal organelle and often involves adherence throughout the cell body (double arrows in E and F). Images in A–C reproduced with permission from the Microbiology Society [2] (A), Elsevier [1] (B), and Wiley and Sons [3] (C).

Figure 2.

Schematic of the Mycoplasma genitalium genome showing the MgPa operon containing the adjacent mgpB and mgpC genes, the 9 homologous MgPar sequences and the mechanism of segmental reciprocal exchange between mgpBC and the MgPar sites. Variable regions B (brown), EF (red), and G (yellow) in mgpB and variable region KLM in mgpC (blue) are separated by conserved regions (black) found only in the mgpB and mgpC genes. Truncated but divergent copies of these variable regions are also found in the MgPar sites, separated by adenine-thymine-rich sequences found only in the MgPar sites (gray). Reciprocal recombination between short stretches of the mgpBC genes and the MgPar sites (thin black lines) results in antigenic and phase variation of the MgpB and MgpC proteins and replacement of sequences in the MgPar sites with those previously in the mgpBC expression sites, in a process termed segmental reciprocal recombination.