Resistance ofMycoplasma pulmonisto Complement Lysis Is Dependent on the Number of Vsa Tandem Repeats: Shield Hypothesis

Abstract

The Vsa proteins are associated with the virulence of the murine respiratory pathogenMycoplasma pulmonis. The antigens consist of a conserved N-terminal region that is combined with one of several different variable C-terminal regions comprised of tandem repeats.M. pulmonisstrains that produce VsaA with about 40 tandem repeats do not adhere to polystyrene or erythrocytes and are highly resistant to complement killing. Strains that produce VsaA with three tandem repeats adhere strongly to polystyrene and erythrocytes and are highly susceptible to complement killing. We report here that the resistance to complement lysis was not due to a lack of activation of the complement cascade. Isolation and analysis ofM. pulmonisstrains that produced Vsa proteins other than VsaA (VsaG and VsaI) with either long or short repeat regions indicated that adherence to polystyrene and resistance to complement were dependent on the length of the repeat region but not on the Vsa type. Furthermore,M. pulmonisVsa variants were susceptible to the polypeptide pore-forming molecule gramicidin D, independent of the Vsa type and length. Collectively, the data indicate the Vsa proteins nonspecifically mediateM. pulmonissurface interactions and function to sterically hinder access of complement to the mycoplasma cell membrane while permitting access of smaller molecules.