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.

Critical Role of Dispensable Genes inMycoplasma agalactiaeInteraction with Mammalian Cells

“…2) revealed the decisive role played by metabolic functions in the adaptation of M. agalactiae to changing environments. A link between carbon metabolism and pathogenicity in mycoplasmas has already been suggested by several groups (5,(21)(22)(23)36). The availability of a carbon source in vivo and its influence on bacterial pathogenicity has reignited interest in using carbon metabolic pathways as viable targets for antibiotic development (7).…”

Cytotoxicity ofMycoplasma mycoidessubsp.mycoidesSmall Colony Type to Bovine Epithelial Cells

“…Glycerol at physiological concentrations is incorporated and phosphorylated by M. mycoides subsp. mycoides SC via the highly active ATP-binding cassette glycerol transporter composed of GtsA, GtsB, and GtsC and is finally converted to dihydroxyacetone phosphate and H 2 O 2 by GlpO (13,18). The gene glpO was found to be present and functional in all M. mycoides subsp.…”

“…Some cytotoxicity in these strains, however, can still be demonstrated upon extended incubation in the presence of glycerol. The low levels of cytotoxicity of these strains may be due to a residual production of H 2 O 2 originating from the metabolism of glycerol that penetrates the mycoplasmas by passive diffusion or via the linear bypass uptake system conferred by the glycerol facilitator gene glpF (13,14,18). The low cytotoxicities of the strains isolated from the European outbreaks in 1980 to 1999 correlate with the lower virulence of this group of strains, as determined by experimental infections (1,12), and reflect the more chronic aspects of CBPP with low mortality rates during these outbreaks (11).…”

“…Since M. mycoides subsp. mycoides SC seems to secrete toxic substances that act only over short distances, such as H 2 O 2 , adhesion is particularly important for an intimate interaction with host cells, which is considered an early step of pathogenesis for most microorganisms (13). Therefore, we tested the adhesion properties of type strain PG1 compared to those of the virulent strain Afadé.…”

“…This showed that glycerol metabolism-dependent H 2 O 2 production represents one of the major virulence attributes of M. mycoides subsp. mycoides SC (13,14).…”