Interaction of Mycoplasma genitalium with host cells: evidence for nuclear localization

Abstract

Mycoplasma genitalium (Mg) is a mollicute that causes a range of human urogenital infections. A hallmark of these bacteria is their ability to establish chronic infections that can persist despite completion of appropriate antibiotic therapies and intact and functional immune systems. Intimate adherence and surface colonization of mycoplasmas to host cells are important pathogenic features. However, their facultative intracellular nature is poorly understood, partly due to difficulties in developing and standardizing cellular interaction model systems. Here, we characterize growth and invasion properties of two Mg strains (G37 and 1019V). Mg G37 is a high-passage laboratory strain, while Mg 1019V is a low-passage isolate recovered from the cervix. The two strains diverge partially in gene sequences for adherence-related proteins and exhibit subtle variations in their axenic growth. However, with both strains and consistent with our previous studies, a subset of adherent Mg organisms invade host cells and exhibit perinuclear targeting. Remarkably, intranuclear localization of Mg proteins is observed, which occurred as early as 30 min after infection. Mg strains deficient in adherence were markedly reduced in their ability to invade and associate with perinuclear and nuclear sites.

Mycoplasma genitalium: a brief review

“…The minimum set of genes, also called essential genes, in both prokaryotes and eukaryotes, are those described as indispensable for the survival of an organism and are therefore the basis of life for a particular organism. 25 identified only 480 protein-coding regions, while a later study by Ueno et al (2008) 3 found 484 coding regions. These identified coding regions include genes for DNA replication, transcription, translation, DNA repair, cellular transport and energy metabolism.…”

“…Following entry into the target cell, the organism appears to reside in the membrane-bound vacuoles closer to the target cell nucleus. 3,4 This internuclear localisation process may take place within 30 minutes after infection.…”

“…36 Virulence M. genitalium has several virulence factors that are responsible for its pathogenicity. These include the ability to adhere to host epithelial cells using the terminal tip organelle with its adhesins, the release of enzymes 3,4 and the ability to evade the host immune response by antigenic variation. 37 …”

“…Although surface-exposed, these adhesins are linked to the internal cytoskeleton of the tip organelle. 3 Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) of mutant strains that are incapable of haemadsorption has been widely used for the characterisation of proteins involved in adhesion. 39 A total of 21 putative protein genes have been identified in the M. genitalium genome, but only a few have been characterised as adhesions.…”

“…The G-37 isolate has become an American Type Culture Collection (ATCC 33530) strain with its genome being fully sequenced in 1995. 3 Due to its slow cell replication and fastidious growth requirements, culture is not usually used for laboratory diagnosis of M. genitalium, hence few epidemiological studies were done in the years following its discovery. However, after the introduction of molecular diagnostic assays, many clinical studies were performed, mainly in developed countries.…”