Ureaplasmas in pathogen-host interactions

Despite colonization of the lower urogenital tract, ureaplasmas reach the upper genital tract only in a subpopulation of women, and only some of these individuals are expressing clinical symptoms. This implicates that only certain ureaplasma subtypes are truly associated with infection and diseae. Accumulating evidence suggests that the ureaplasma multiple-banded antigen (MBA) is likely to be a pivotal mediator in the interaction of ureaplasmas with their host cells. Within individual ureaplasma serovars, the MBA has been shown to be present in different sizes representing an additional level of genetic variability beyond the serovar category which may contribute to ureaplasma pathogenesis. The phenomenon of protein size variation resulting from changes in repetitive structures has been deciphered in other mycoplasma species, but little is known regarding its significance and its function in the host. Recent data have demonstrated that the simple structure of MBA contains a diversity of immunoreactive sequences which could provide an advantage in avoiding the host immune response and in establishing a successful infection in a changing microenvironment during infection. The proposed project will determine the exact contribution of the MBA to ureaplasma pathogenesis by assessing its participation in promoting cell attachment, cell invasion and transcellular passage of human endometrial cells. In addition, appropriate test methods for detection and characterization of MBA variation and its putative role in adherence and adherence modulation will be established. The feasibility of such experiments is now ensured because of the recent break through in ureaplasma cultivation yielding much larger colonies on agar plates. The project will also provide information about the possible relevance and significance of environmental host signals in ureaplasma virulence expression and variation. Taken collectively, it is expected that the information accumulated in these studies will ultimately lead to novel insights into the currently unknown molecular pathways of pathogenesis enabling ureaplasmas to cytadhere and to penetrate mucosal barriers resulting in invasive and disseminated disease patterns.

Despite colonization of the lower urogenital tract, ureaplasmas reach the upper genital tract only in a subpopulation of women, and only some of these individuals are expressing clinical symptoms. This implicates that only certain ureaplasma subtypes are truly associated with infection and diseae. Accumulating evidence suggests that the ureaplasma multiple-banded antigen (MBA) is likely to be a pivotal mediator in the interaction of ureaplasmas with their host cells. Within individual ureaplasma serovars, the MBA has been shown to be present in different sizes representing an additional level of genetic variability beyond the serovar category which may contribute to ureaplasma pathogenesis. The phenomenon of protein size variation resulting from changes in repetitive structures has been deciphered in other mycoplasma species, but little is known regarding its significance and its function in the host. Recent data have demonstrated that the simple structure of MBA contains a diversity of immunoreactive sequences which could provide an advantage in avoiding the host immune response and in establishing a successful infection in a changing microenvironment during infection. The proposed project will determine the exact contribution of the MBA to ureaplasma pathogenesis by assessing its participation in promoting cell attachment, cell invasion and transcellular passage of human endometrial cells. In addition, appropriate test methods for detection and characterization of MBA variation and its putative role in adherence and adherence modulation will be established. The feasibility of such experiments is now ensured because of the recent break through in ureaplasma cultivation yielding much larger colonies on agar plates. The project will also provide information about the possible relevance and significance of environmental host signals in ureaplasma virulence expression and variation. Taken collectively, it is expected that the information accumulated in these studies will ultimately lead to novel insights into the currently unknown molecular pathways of pathogenesis enabling ureaplasmas to cytadhere and to penetrate mucosal barriers resulting in invasive and disseminated disease patterns.