Phase variations of the Mycoplasma penetrans main surface lipoprotein increase antigenic diversity

Mycoplasma penetrans is a recently identified mycoplasma, isolated from uri ne samples collected from human immunodeficiency virus (HIV)-infected patie nts. Its presence is significantly associated with HIV infection. The major antigen recognized during natural and experimental infections is an abunda nt P35 lipoprotein which, upon extraction, segregates in the Triton X-114 d etergent phase and is the basis of M. penetrans-specific serological assays . We report here that the P35 antigen undergoes spontaneous and reversible phase variation at high frequency, leading to heterogeneous populations of mycoplasmas, even when derived from a clonal lineage. This variation was fo und to be determined at the transcription level, and although this property is not unique among the members of the class Mollicutes, the mechanism by, which it occurs in M. penetrans differs from those previously described for other Mycoplasma species. Indeed, the P35 phase variation was due neither to a p35 gene rearrangement nor to point mutations within the gene itself o r its promoter. The P35 phase variation in the different variants obtained was concomitant with modifications in the pattern of other expressed lipopr oteins, probably due to regulated expression of selected members of a gene family which was found to potentially encode similar lipoproteins. M. penet rans variants could be selected on the basis of their lack of colony immuno reactivity with a polyclonal antiserum against a Triton X-114 extract, stro ngly suggesting that the mechanisms involved in altering surface antigen ex pression might allow evasion of the humoral immune response of the infected host.