ELONGATED VERSIONS OF VLP SURFACE LIPOPROTEINS PROTECT MYCOPLASMA-HYORHINIS ESCAPE VARIANTS FROM GROWTH-INHIBITING HOST ANTIBODIES

Variation in Vlp surface proteins of Mycoplasma hyorhinis was evaluate d in terms of its role in determining susceptibility of organisms to g rowth inhibition by host antibodies (Abs), High-frequency switching of Vip surface lipoproteins has been studied in isogenic lineages of M. hyorhinis SK76, In these lineages, the products of three genes, vlpA, vlpB, and vlpC, are subject to phase and size variation in vitro, whic h occur through distinct mutator elements that independently govern th e expression of each vlp gene (promoter mutations) or the size of the rip gene product (by intragenic expansion or contraction of a 3' regio n containing tandem repeats), Isogenic clonal variants of M. hyorhinis SK76 expressing distinct profiles of Vip products were assessed for t heir susceptibility to complement-independent growth inhibition by ser um Abs of swine experimentally infected with the arthritigenic SK76 st rain, Invariably, variants expressing longer versions of VlpA, VlpB, o r VlpC (each expressed individually) were completely resistant to host immune serum Abs, whereas variants expressing shorter allelic version s of each Vlp were susceptible, The target of growth-inhibiting Abs wa s not the Vip products, since removal of anti-Vlp Abs had no effect on the inhibitory activity of the host immune serum on susceptible varia nts, Escape variant populations derived by propagating susceptible var iants in an immune (versus control) host serum revealed a strong selec tion for the long-Vlp phenotype, irrespective of the identity of the V lp expressed. Apparent mutational pathways of acquiring the protective phenotype included mutational switches to express long rip genes that had been transcriptionally silent or switches to elongate expressed v lp genes, These results suggest that a major function of the Vip syste m is to shield the wall-less mycoplasma surface from host Abs capable of binding vital (and as-yet-unidentified) surface antigens of this or ganism.