Molecular basis of size and antigenic variation of a Mycoplasma hominis adhesin encoded by divergent vaa genes

Abstract

The molecular basis for the size and antigenic diversity of the variable adherence-associated (Vaa) antigen, a major surface protein and a putative adhesin of Mycoplasma hominis, is described. Size-variant alleles of the single-copy vaa gene encode abundant surface lipoproteins containing one to four nearly identical, tandem repetitive units of 121 amino acids in the central region of the mature Vaa product. Gain or loss of central repeats in vaa genes gives rise to distinct size-variant Vaa antigens in clonal populations of this organism. The N-terminal and repeat regions of Vaa contain highly conserved sequences, while the C-terminal region, implicated as the adherence-mediating module, is highly variable and divergent among different strains of this pathogen. Sequence variation in this region may underlie the strain-dependent binding of some monoclonal antibodies to Vaa products. The Vaa antigen is expressed in vivo during chronic, active arthritis associated with M. hominis infection and is highly immunogenic in the human host. Size variation and C-terminal antigenic divergence of Vaa could affect the adherence of M. hominis and evasion of antibody-mediated immunity, thereby contributing to the organism's adaptive capability in the human host. Variation in vaa genes reveals a distinct pattern of mutations generating mycoplasma surface variation.