SUMMARY The recent sequencing of the entire genomes of Mycoplasma genitalium and M. pneumoniae has attracted considerable attention to the molecular biology of mycoplasmas, the smallest self-replicating organisms. It appears that we are now much closer to the goal of defining, in molecular terms, the entire machinery of a self-replicating cell. Comparative genomics based on comparison of the genomic makeup of mycoplasmal genomes with those of other bacteria, has opened new ways of looking at the evolutionary history of the mycoplasmas. There is now solid genetic support for the hypothesis that mycoplasmas have evolved as a branch of gram-positive bacteria by a process of reductive evolution. During this process, the mycoplasmas lost considerable portions of their ancestors’ chromosomes but retained the genes essential for life. Thus, the mycoplasmal genomes carry a high percentage of conserved genes, greatly facilitating gene annotation. The significant genome compaction that occurred in mycoplasmas was made possible by adopting a parasitic mode of life. The supply of nutrients from their hosts apparently enabled mycoplasmas to lose, during evolution, the genes for many assimilative processes. During their evolution and adaptation to a parasitic mode of life, the mycoplasmas have developed various genetic systems providing a highly plastic set of variable surface proteins to evade the host immune system. The uniqueness of the mycoplasmal systems is manifested by the presence of highly mutable modules combined with an ability to expand the antigenic repertoire by generating structural alternatives, all compressed into limited genomic sequences. In the absence of a cell wall and a periplasmic space, the majority of surface variable antigens in mycoplasmas are lipoproteins. Apart from providing specific antimycoplasmal defense, the host immune system is also involved in the development of pathogenic lesions and exacerbation of mycoplasma induced diseases. Mycoplasmas are able to stimulate as well as suppress lymphocytes in a nonspecific, polyclonal manner, both in vitro and in vivo. As well as to affecting various subsets of lymphocytes, mycoplasmas and mycoplasma-derived cell components modulate the activities of monocytes/macrophages and NK cells and trigger the production of a wide variety of up-regulating and down-regulating cytokines and chemokines. Mycoplasma-mediated secretion of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1 (IL-1), and IL-6, by macrophages and of up-regulating cytokines by mitogenically stimulated lymphocytes plays a major role in mycoplasma-induced immune system modulation and inflammatory responses.

In an enzyme-linked immunosorbent assay (ELISA) for detection of IgM antibodies to Toxoplasma gondii, sera from individuals with negative results in the Sabin-Feldman dye test (DT) and sera from individuals with chronic toxoplasma infection all yielded negative results, even when tested undiluted. In contrast, of sera obtained from individuals with recently acquired toxoplasmosis, all sera that gave positive results in both the DT and the IgM-immunofluorescent antibody (IgM-IFA) test and 92.8% of sera that gave negative results in the IgM-IFA test yielded strongly positive results in the IgM-ELISA. Thus, the IgM-ELISA is more sensitive than the IgM-IFA test in the diagnosis of recently acquired infection with T. gondii. Moreover, sera that gave negative results in the DT but that contained either antinuclear antibodies or rheumatoid factor and thus caused false-positive results in the IgM-IFA test all yielded negative results in the IgM-ELISA, probably because serum IgM and IgG fractions were separated during the initial step.

We have attempted to define the serologic criteria for diagnosis of toxoplasmosis in heart transplant recipients. Of 31 patients who were seronegative before transplantation, 4 received a heart from a seropositive donor, and 3 of these 4 had seroconversion and developed life-threatening toxoplasmosis; the remaining 27 did not have seroconversion or develop clinical toxoplasmosis. Of 19 patients who had antibodies to Toxoplasma before transplantation, 10 developed significant increases in test titers of the dye test or double-sandwich IgM enzyme-linked immunosorbent assay but did not develop a clinical illness that could be attributed to toxoplasma infection. Significant serologic changes occurred more often in patients who received azathioprine, corticosteroids, and antithymocyte globulin than in those who received cyclosporine, corticosteroids, and antithymocyte globulin (p less than 0.05). These data show the wide clinical spectrum and differences in kinetics of antibody response of patients who develop toxoplasma infection after transplantation, and suggest that clinical disease occurs in those who have seroconversion but is rare in patients with preexisting antibody who have serologic evidence of recrudescence.

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