Mycoplasma arthritidis is a natural pathogen of rats. Although natural infections are now rare, experimental arthritis can be induced by intravenous or intraperitoneal injections. The resulting disease is characterized by rapid onset of acute, inflammatory polyarthritis, followed by a chronic, nonmigratory phase lasting six weeks or longer in some animals. This disease has been used extensively in the past as a model for studying human arthritis, and it remains a convenient and inexpensive system for examining certain inflammatory and immunologic aspects. This study will focus on two M. arthritidis surface lipoproteins, MAA1 and MAA2, both of which contribute to adherence to host tissue, are highly immunogenic for infected animals, and induce protective immunity in rats. The central hypothesis is that these proteins are important in pathogenesis of M. arthritidis-induced arthritis, possibly by mediating or facilitating adherence to rat tissues. This study will further define their roles in this process.
The first aim of this proposal is to prepare genetic constructs to be used in testing this hypothesis. Mutants will be constructed in which the genes encoding both proteins are disrupted by transposon mutagenesis. These mutants will then be subjected to genetic complementation to reintroduce wild-type alleles of the disrupted genes.
The second aim i s to test these mutants and their genetically complemented counterparts for the ability to attach to rat cells in vitro and to induce arthritis in rats. This study will help to establish the function of these important proteins in the pathogenesis of M. arthritidis-induced arthritis. This, in turn, will provide insight into how similar events may occur in inflammatory joint diseases of humans and other animals. ? ?
| Bird, Daniel W; Graber, Kelly; Knutson, Allison et al. (2008) Mutation of two Mycoplasma arthritidis surface lipoproteins with divergent functions in cytadherence. Infect Immun 76:5768-76 |
