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.

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Structure, Size, and Base Composition .427 Genome Replication .428 Irradiation Damage and Repair .429 Mycoplasma Genetics .430 RIBOSOMAL AND TRANSFER RIBONUCLEIC ACIDS .430 CELL MEMBRANE.432 Membrane Isolation .432 Capsules.......... 433 MEMBRANE LIPIDS .434 Lipid Composition .434 Phospholipids .434 Glycolipids .434 Lipopolysaccharide .435 Fatty acids .435 Cholesterol .435

The biological properties and special characteristics of the human T mycoplasmas have been reviewed and summarized. The T mycoplasmas are distinguished from all other known mycoplasmas by their production of urease, and, therefore, by their ability to hydrolyze urea. This singular property significantly sets the T mycoplasmas apart from all other members of the order Mycoplasmatales. In consideration of this distinguishing property, it is reasonable to propose establishing a new, separate genus in the family Mycoplasmataceae in which t o classify the T mycoplasmas isolated from man and lower animals. The name Ureaplasma is proposed for this new genus, which at present contains a single human species of at least eight different serotypes. The name Ureaplasma urealyticum is proposed for this new species. The type strain of U. urealyticum is human strain 960-(CX8), serotype VIII (Black); it has been deposited in the American Type Culture Collection as ATCC 27618.T mycoplasmas were first recognized and identified in 1954 in primary agar cultures of urethral exudates from male nongonococcal urethritis patients. They were called "tiny-form PPLO" (pleuropneumonia-like organisms) and "T-form colonies of PPLO" after the minute size, distinctive characteristics, and morphology of their agar colonies. The first published reference to these unusual mycoplasmas was a brief description accompanying two photomicrographs of "T" colonies in a primary agar culture of urethral exudate (53). Subsequent studies confirmed that T mycoplasmas were new, previously undescribed members of the human mycoplasma group. Their distinctive morphology and cultural characteristics were described and illustrated in detail in 1956 (54).The original minute colony size (10 * 5 pm) was the result of nutritionally inadequate culture media of distinctly unfavorable alkaline reaction (pH 7.8 to 8.0) resulting in near threshold performance in supporting growth of T mycoplasmas. Some of the early failures of other investigators t o isolate T mycoplasmas from clinical exudates may also be explained by the incorporation by these investigators of thallium acetate in the medium in accordance with standard classical mycoplasma methodology. This antibacterial agent is almost completely inhibitory t o many strains of T mycoplasmas in primary agar cultures in alkaline media of pH 7.8 t o 8.0. Thallium acetate was never employed in Shepard's laboratory , where only penicillin was incorporated as an antibacterial agent (1,000 U/ml).Prior to 1966, identification of T mycoplasmas in primary cultures was limited exclusively to characteristic minute size, morphology, and staining reaction of agar colonies. The subsequent development of improved agar culture media made identification based upon the above-mentioned criteria less reliable, since T colonies were no longer really "tiny." Identification was especially difficult under conditions of crowding in mixed mycoplasma cultures since classical mycoplasma colonies often completely lost the ability to produce the surface...

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