Elongated versions of Vlp surface lipoproteins protect Mycoplasma hyorhinis escape variants from growth-inhibiting host antibodies

Abstract

Variation in Vlp surface proteins of Mycoplasma hyorhinis was evaluated in terms of its role in determining susceptibility of organisms to growth inhibition by host antibodies (Abs). High-frequency switching of Vlp 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, which occur through distinct mutator elements that independently govern the expression of each vlp gene (promoter mutations) or the size of the vlp gene product (by intragenic expansion or contraction of a 3 region containing tandem repeats). Isogenic clonal variants of M. hyorhinis SK76 expressing distinct profiles of Vlp products were assessed for their susceptibility to complement-independent growth inhibition by serum Abs of swine experimentally infected with the arthritigenic SK76 strain. Invariably, variants expressing longer versions of VlpA, VlpB, or VlpC (each expressed individually) were completely resistant to host immune serum Abs, whereas variants expressing shorter allelic versions of each Vlp were susceptible. The target of growth-inhibiting Abs was not the Vlp products, since removal of anti-Vlp Abs had no effect on the inhibitory activity of the host immune serum on susceptible variants. Escape variant populations derived by propagating susceptible variants in an immune (versus control) host serum revealed a strong selection for the long-Vlp phenotype, irrespective of the identity of the Vlp expressed. Apparent mutational pathways of acquiring the protective phenotype included mutational switches to express long vlp genes that had been transcriptionally silent or switches to elongate expressed vlp genes. These results suggest that a major function of the Vlp system is to shield the wall-less mycoplasma surface from host Abs capable of binding vital (and as-yet-unidentified) surface antigens of this organism.

Phase Variations of the Mycoplasma penetrans Main Surface Lipoprotein Increase Antigenic Diversity

“…Second, it has been shown in vitro that, using as a selection pressure MAbs or antibodies from immunized or experimentally infected animals directed against surface antigens, it is possible to drive the antigenic variation in M. bovis (23). Third, M. hyorhinis variants expressing Vlp (variable lipoprotein) extended in length were resistant to complementindependent growth inhibition by host antibodies, whereas variants expressing shorter Vlp are more susceptible (9). Our data confirm the phase variations of immunodominant lipoproteins in mycoplasmas.…”

Localized reversible frameshift mutation in an adhesin gene confers a phase‐variable adherence phenotype in mycoplasma

“…The intricacy of mycoplasma surface variation is further highlighted by high-frequency phase variation involving alteration in the accessibility of epitopes on surface lipoproteins (as opposed to variation in expression of these products; Rosengarten and Yogev, 1996;Theiss et al, 1996). This is postulated to occur through phase variation in the expression of masking components (Theiss et al, 1996;Citti et al, 1997).…”

Recognition of Mycoplasma hyorhinis by CD99‐Fc molecule

“…Furthermore, pronounced CD99-Ig staining was induced by infection of two out of five other laboratory strains of M. hyorhinis (PG 42 and NIH 1, data not shown). The fact that binding was lost after several passages in culture and that CD99-Ig recognizes two out of the five laboratory strains of M. hyorhinis is most probably due to the well-known phenotypic switching phenomena described in M. hyorhinis [41,42]. Thus, the ligand recognized by CD99-Ig is specific to M. hyorhinis and might be manipulated by antigenic variation of the mycoplasma.…”