Molecular mechanisms of pathogenicity of Mycoplasma mycoides subsp. mycoides SC

Abstract

Mycoplasma mycoides subsp. mycoides SC, the aetiological agent of contagious bovine pleuropneumonia (CBPP), is considered the most pathogenic of the Mycoplasma species. Its virulence is probably the result of a coordinated action of various components of an antigenically and functionally dynamic surface architecture. The different virulence attributes allow the pathogen to evade the host's immune defence, adhere tightly to the host cell surface, persist and disseminate in the host causing mycoplasmaemia, efficiently import energetically valuable nutrients present in the environment, and release and simultaneously translocate toxic metabolic pathway products to the host cell where they cause cytotoxic effects that are known to induce inflammatory processes and disease. This strategy enables the mycoplasma to exploit the minimal genetic information in its small genome, not only to fulfil the basic functions for its replication but also to damage host cells in intimate proximity thereby acquiring the necessary bio-molecules, such as amino acids and nucleic acid precursors, for its own biosynthesis and survival.

Fig. 1

Schematic representation of the various virulence pathways of M. mycoides subsp. mycoides SC. The mycoplasma is represented in yellow, the host cells in light blue. The upper pathway, which is currently the best characterized, is based on glycerol import and metabolism. GtsABC represents the membrane-located ATP-binding cassette (ABC) transporter system, which incorporates and phosphorylates imported glycerol to glycerol-3-phosphate (G3P). The bypass pathway that allows diffusion of glycerol via the glycerol facilitator factor (GlpF) and the subsequent phosphorylation by the glycerol kinase (GlpK) has not been evidenced directly, but the corresponding genes, glpF and glpK, have been found by cloning and DNA sequence analysis, and their functionality was supported by strains lacking functional gtsABC genes, which can import and phosphorylate glycerol. The membrane-located l-α-glycerophosphate oxidase (GlpO) represents the central enzyme in this virulence pathway and is able to translocate H₂O₂ or reactive oxygen species (ROS) into the host cell. The adhesins that seem necessary for the close contact are still hypothetical. The variable surface antigen (Vmm) is supposed to play a role in evading the host’s immune defence. Capsular polysaccharide has been proposed to be produced by most Mycoplasma species and is expected to induce cytokine production. Lipoprotein LppQ is highly antigenic and also seems to be involved in the induction of inflammatory processes by superantigen-like properties. Catabolism of glucosides by the phosphotransferase system (PTS) and 6-phospho-β-glucosidase (Bgl) is known to repress virulence of many pathogens.