The mechanisms by which AIDS-related mycoplasmas interact with host cells will be assessed. The use of available mycoplasma DNA and antibody probes will permit the identification of putative adhesin genes associated with these mycoplasmas. Implicated genes will be cloned and sequenced, and correlations between known adhesins of Mycoplasma pneumoniae and those of M. fermentans, M. pirum and M. genitalium, will be examined. Based upon preliminary data it appears that a family of adhesin-related genes exist among these mycoplasmas, and that expression of these genes may regulate mycoplasma-host cell interactions nd mycoplasma virulence potential. Also, cytadherence-mediating epitopes will be identified using antibodies generated against the AIDS-related mycoplasmas and several expression vector systems. In addition, these experimental approaches will be used to characterize immunodominant epitopes and possible sequence divergency among the AIDS-related mycoplasma adhesins as reported by us for the P1 adhesin of M. pneumoniae. the use of several eucaryotic cell systems, including human lung and brain cells, along with ultrastructural and immunologic techniques, should assist in defining cytadherence mechanisms. Subsequent biological events that follow the host-mycoplasma interaction will be monitored, including possible mycoplasma penetration and intracellular residence and host cell cytopathology. Spontaneously arising noncytadhering mutants of M. fermentans, M. pirum and M. genitalium will be isolated and characterized for adhesin-associated biochemical and genetic deficiencies. Lastly, preliminary data suggest an increased immunoresponsiveness to M. fermentans strain incognitus (Mi) by HIV+ individuals prior to and during the development of AIDS-related symptoms. therefore, the dissection of mycoplasma-host cell interactions and the identification of adhesin genes and their products may provide useful reagents for the diagnosis of AIDS-progression, the evaluation of various therapies and the development of rational vaccine candidates.
