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Association of Mycoplasma arthritidis mitogen with lethal toxicity but not with arthritis in mice.

ABSTRACT: Mycoplasma arthritidis induces an acute to chronic arthritis in rodents. Arthritis induced in mice histologically resembles human rheumatoid arthritis and can be associated with lethal toxicity following systemic injection. The M. arthritidis mitogen (MAM) superantigen has long been implicated as having a role in pathogenesis, but its significance with respect to toxicity and arthritogenicity in mycoplasma-induced disease is unclear. To study the pathogenic significance of MAM, M. arthritidis mutants that overproduced or failed to produce MAM were developed. MAM overproduction and knockout mutants were more and less mitogenic, respectively, than the wild-type strain. The degree of mitogenic activity correlated with lethal toxicity in DBA/2J mice. In contrast, histopathological studies detected no correlation between MAM production and the severity of arthritis induced in DBA/2J and CBA/J mice.

SUBMITTER: Luo W

PROVIDER: S-EPMC2573368 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Association of Mycoplasma arthritidis mitogen with lethal toxicity but not with arthritis in mice.

Luo Wenyi W Yu Huilan H Cao Zuhua Z Schoeb Trenton R TR Marron Michele M Dybvig Kevin K

Infection and immunity 20080908 11

Mycoplasma arthritidis induces an acute to chronic arthritis in rodents. Arthritis induced in mice histologically resembles human rheumatoid arthritis and can be associated with lethal toxicity following systemic injection. The M. arthritidis mitogen (MAM) superantigen has long been implicated as having a role in pathogenesis, but its significance with respect to toxicity and arthritogenicity in mycoplasma-induced disease is unclear. To study the pathogenic significance of MAM, M. arthritidis mu ...[more]

PMID: 18779340

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Design of PCR-based method for detection of a gene-encoding Mycoplasma arthritidis mitogen superantigen in synovial fluid of rheumatoid arthritis patients.

Project description:BACKGROUND AND OBJECTIVES:Mycoplasma arthritidis mitogen (MAM) superantigen has been shown to induce chronic arthritis, which resembles human rheumatoid arthritis (RA) in a rodent model. However, its role as a causative agent in human RA is not well understood yet. The aim of this study was to investigate the presence of MAM superantigen gene in the synovial fluid (SF) of RA patients. MATERIALS AND METHODS:The MAM superantigen gene a reference was synthesized based on GenBank Data base (Gene ID: 6418105). Specific primer pairs were designed and PCR amplification was performed for MAM superantigen gene detection. A total of 133 SF samples of RA patients were assayed. The PCR products were subjected to sequencing and were descriptively analyzed. RESULTS:The results of the PCR product sequencing showed the method has objective applicability and accuracy. The sensitivity of the PCR reaction for the reference DNA template was 1ng/ml. The PCR results assay of the 133 SF samples raveled that, 9.7% and 22.5% of them were positive for the MAM superantigen gene and Mycoplasma pneumoniae (M. pneumoniae), respectively. CONCLUSION:In this study, two Mycoplasma genomes were detected with increased frequency in RA SF patients' samples. This finding appears to be a promising instrument in the etiological diagnostic of RA patients and could also lead to improved treatment selection. Further research on the other Mycoplasma species present in the SF of RA patients is essential.

| S-EPMC4411428 | biostudies-literature

Genome of Mycoplasma arthritidis.

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Crystal structure of the Mycoplasma arthritidis-derived mitogen in apo form reveals a 3D domain-swapped dimer.

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Molecular characterization of Mycoplasma arthritidis membrane lipoprotein MAA1.

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Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex.

Project description:Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing particular TCR Vbeta elements. Here we report the crystal structure of MAM complexed with a major histocompatibility complex (MHC) antigen, HLA-DR1, loaded with haemagglutinin peptide 306-318 (HA). The structure reveals that MAM has a novel fold composed of two alpha-helical domains. This fold is entirely different from that of the pyrogenic superantigens, consisting of a beta-grasped motif and a beta barrel. In the complex, the N-terminal domain of MAM binds orthogonally to the MHC alpha1 domain and the bound HA peptide, and to a lesser extent to the MHC beta1 domain. Two MAM molecules form an asymmetric dimer and cross-link two MHC antigens to form a plausible, dimerized MAM-MHC complex. These data provide the first crystallographic evidence that superantigens can dimerize MHC molecules. Based on our structure, a model of the TCR2MAM2MHC2 complex is proposed.

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Molecular characterization of Mycoplasma arthritidis variable surface protein MAA2.

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Characterization of the lysogenic bacteriophage MAV1 from Mycoplasma arthritidis.

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| S-EPMC107667 | biostudies-literature

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Mutation of two Mycoplasma arthritidis surface lipoproteins with divergent functions in cytadherence.

Project description:Mycoplasma arthritidis is a natural pathogen of rats, causing an acute polyarthritis. Previous studies identified two membrane-bound lipoproteins, Maa1 and Maa2, thought to be associated with cytadherence of M. arthritidis strain 158p10p9. We have since confirmed that Maa1 is a major adhesin, although the role of Maa2 has proven more elusive. Both proteins were capable of eliciting protective immunity in rats against challenge with the virulent strain 158p10p9, suggesting that they may be important in pathogenesis. The purpose of this study was to better understand the roles of Maa1 and Maa2 in cytadherence in vitro. Insertion mutants were created for both genes by transposon mutagenesis. In vitro adherence of the Maa1 mutant KOMaa1 to rat L2 lung cells was reduced to the level previously reported for a spontaneous low-adherence mutant of 158p10p9 in which Maa1 is truncated and nonfunctional. Surprisingly, adherence of the Maa2 mutant KOMaa2 was approximately fivefold greater than that of the wild type. Complementation of KOMaa1 and KOMaa2 with wild-type alleles of maa1 and maa2, respectively, returned adherence to wild-type levels. This work confirms our earlier observation that Maa1 is a major adhesin for M. arthritidis strain 158p10p9. Maa2, on the other hand, may play a suppressive or modulatory role, possibly serving to release organisms from microcolonies at certain stages of infection.

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