Molecular basis of Mycoplasma gallisepticum pathogenicity

Mycoplasmas are wall-less bacteria, of which some species represent important pathogens in both medicine and agriculture. Because studies of the molecular basis of mycoplasma pathogenicity lag far behind those of other bacterial pathogens, their strategies of infection and disease are not well understood. This project uses the avian pathogen Mycoplasma gallisepticum as model organism in better understanding mycoplasma pathogenesis at the cellular and molecular levels. It is proposed to determine the molecular players directly or indirectly involved in attachment of this organism to its host cells by applying molecular techniques combined with immunostaining procedures and electron microscopy. Detailed analysis of the structure, cellular localization and interaction of Mycoplasma gallisepticum cytadhesins and related products, and of the morphological features as well as the cell- adhesive and cell-invasive properties by which Mycoplasma gallisepticum mutants differ from one another will lead to some significant insights about the molecular basis of pathogenicity of this organism. Taken collectively, it is expected from these studies to define the contribution of well-defined and less-characterised cytadhesins and accessory molecules of Mycoplasma gallisepticum to host cell interactions by assessing their participation in forming the attachment organelle and in promoting cell attachment and cell invasion. Data and reagents accumulated with these studies will allow the design of future in vivo experiments using the natural host, the chicken, to determine the exact role of the various cytadhesins and related components of Mycoplasma gallisepticum in initiating colonization and in establishing local and systemic infection and disease. In addition, this project will establish the groundwork for other areas of investigation relating to the pathogenic pathways of the phylogenetically closely related human pathogen Mycoplasma pneumoniae which seems to use similar strategies for colonization but lacks an appropriate animal model necessary for pathogenesis studies.

The poultry pathogen Mycoplasma gallisepticum has proved to be a suitable model organism to advance our understanding of mycoplasma pathogenesis at the cellular and molecular levels and to get more insight into the strategies of infection and disease caused by these wall-less bacteria. By applying molecular techniques combined with immunostaining procedures and electron microscopy, it appears that at least some of the molecular players directly or indirectly involved in host cell attachment and host cell invasion of this organism are encoded by a pathogenicity island-like gene locus, the so-called mgc gene cluster. The development of immunological reagents to monitor the expression and variation of these key molecules in vitro and in vivo, and first progress towards the construction of shuttle vectors for targeted gene disruption and gene complementation are important steps forward which set up the basis for more refined follow-up studies to assess the exact function of the mgc gene locus and its various gene products in M. gallisepticum infection and disease. The observation that M. gallisepticum is able to invade chicken red blood cells represents a major breakthrough in mycoplasma molecular pathogenesis research in general and paves the way for future investigations relating to the pathogenic pathways and molecular infection biology of this particular agent as well as of other pathogenic mycoplasmas which seem to use similar strategies for host colonization.