Mycoplasma arthritidis Pathogenicity: Membranes, MAM, and MAV1

Washburn, Leigh Rice; Cole, Barry C.

doi:10.1007/0-306-47606-1_21

Cited by 6 publications

(6 citation statements)

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“…For this reason, our finding that M. arthritidis, a naturally occurring, well-characterized pathogen of mice and rats, also possesses a macrophage-activating component(s) which utilizes TLR2 provides a very useful model to determine the role of TLR2-ligand interactions in mycoplasma-mediated inflammatory disease. The mechanisms of pathogenesis of M. arthritidis-mediated inflammatory disease are no less complex than those of many other microbial diseases (6,53). In addition to the TLR2-dependent macrophage-activating moiety found here, we recently showed that the MAM superantigen not only displays typically superantigenic interactions with specific MHC molecules and T-cell receptors (7) but also uniquely activates macrophages through an interaction with both TLR2 and TLR4.…”

Section: Discussionmentioning

confidence: 63%

“…The M. arthritidis model of inflammatory disease has been extensively studied in our laboratories (6,53) and that of others, resulting in the identification of animal strains that differ in their susceptibility to disease as well as the identification and derivation of organisms exhibiting differing degrees of virulence. Mycoplasma arthritidis is a natural pathogen of rodents that can induce an acute or chronic arthritis.…”

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confidence: 99%

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Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components fromMycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2

Cole

Pennock

et al. 2005

Infect Immun

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Mycoplasma arthritidis induces toxicity, arthritis, and dermal necrosis in mice. Virulence factors include a superantigen and membrane adhesins and possibly also a bacteriophage component. Here we compare the biological properties of Triton X-114 extracts derived from avirulent and virulent M. arthritidis strains. Macrophage cell lines and resident peritoneal macrophages were used to assess inflammatory potential as indicated by production of tumor necrosis factor alpha, interleukin-6, and/or nitric oxide. The activity resided exclusively within the hydrophobic detergent phase, was unaffected by heat treatment at 100°C for 30 min, and was resistant to proteinase K digestion, suggesting involvement of a lipopeptide. Contamination of extracts with endotoxin or superantigen was excluded. Extracts of the more virulent strain had higher activity than did those of the avirulent strain. Using CHO cells expressing Toll-like receptor 2 (TLR2) or TLR4, both with transfected CD14, we showed that extracts activated these cells via TLR2 but not by TLR4. Also, macrophages from C57BL/6 TLR2 ؊/؊ mice failed to respond to the extracts, whereas those from TLR2 ؉/؉ cells did respond. The preparations from the virulent strain of M. arthritidis were also more potent in activating dendritic cells, as evidenced by up-regulation of major histocompatibility complex class II, CD40, B7-1, and B7-2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent elution of gel slices revealed the presence of three active moieties which corresponded to molecular masses of approximately 24, 28, and 40 kDa. Three active components were also found by reverse-phase chromatography. We suggest that macrophage activation by M. arthritidis could play a significant role in the inflammatory response induced in the host by this organism.

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Section: Discussionmentioning

confidence: 63%

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confidence: 99%

Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components fromMycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2

Cole

Pennock

et al. 2005

Infect Immun

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“…Disease in mice is more chronic than in rats, with lesions similar to those seen in human rheumatoid arthritis (25). Factors thought to contribute to the virulence of M. arthritidis are MAM, a potent superantigen secreted by the mycoplasma, and the M. arthritidis adhesins (MAAs) that have a role in cytadherence (32).…”

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confidence: 99%

Genome of Mycoplasma arthritidis

et al. 2008

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The genomes of several species of mycoplasma have been sequenced. Most of these species rely on the glycolytic pathway for energy production, with the one exception of Ureaplasma, a species that breaks down urea as its principle source of acquiring energy. Several species, including as Mycoplasma arthritidis, are nonglycolytic and can use arginine as their source of energy. Described here are the genome sequence and a transposon library of M. arthritidis. The genome of 820,453 bp is typical in size for a mycoplasma and contains two large families of genes that are predicted to code for phase-variable proteins. The transposon library was constructed using a minitransposon that inserts stably into the mycoplasma genome. Of the 635 predicted coding regions, 218 were disrupted in a library of 1,100 members. Dispensable genes included the gene coding for the MAM superantigen and genes coding for ribosomal proteins S15, S18, and L15.Mycoplasma arthritidis is a natural pathogen of rats, causing severe polyarthritis. Arthritis in mice can be experimentally induced by injection of M. arthritidis into the tail vein. Disease in mice is more chronic than in rats, with lesions similar to those seen in human rheumatoid arthritis (25). Factors thought to contribute to the virulence of M. arthritidis are MAM, a potent superantigen secreted by the mycoplasma, and the M. arthritidis adhesins (MAAs) that have a role in cytadherence (32).The genome sequences of several species of mycoplasma are known (see http://cbi.labri.fr/outils/molligen/). Other than Ureaplasma, which utilizes the hydrolysis of urea to generate ATP, all of the mycoplasma species that have sequenced genomes are glycolytic. Some species of mycoplasma such as M. arthritidis are nonglycolytic, and thus it was anticipated that the sequence of the M. arthritidis genome would reveal new aspects of mycoplasma physiology. Nonglycolytic mycoplasmas generally catabolize arginine as a major source of energy, and, indeed, the required genes for arginine catabolism were identified in the genome sequence of M. arthritidis.Described here is the genome sequence of the virulent M. arthritidis strain 158L3-1 (3, 31). Strain 158L3-1 is a lysogen containing the 16-kb genome of the MAV1 bacteriophage. No additional prophages were noted in the genome. The sequence revealed features offering insight into the mechanisms by which the mycoplasma causes chronic inflammation, including two families of genes that are predicted to code for phasevariable proteins and a predicted gene product related to but distinct from MAM.We also describe a transposon library of M. arthritidis strain 158, the nonlysogenic parent of 158L3-1. The library was created using minitransposons derived from Tn4001 that inserts into the genome at essentially random sites. The genomic location of the minitransposon was determined for 1,113 library members. Using criteria for gene inactivation previously developed for transposon mutagenesis of Mycoplasma pulmonis, 218 of the predicted protein coding regions, including ...

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“…Despite the apparent association between MAM/TLR usage and the differential effects of anti‐B7‐1 on cytokine production and disease mediated by M. arthritidis, it should be noted that a variety of virulence factors apart from MAM have been described for M. arthritidis (Washburn and Cole, 2002). Recently, we demonstrated that M. arthritidis also contains a cell‐bound, TLR2‐dependent, macrophage‐activating component that may also be associated with disease severity (Cole et al ., 2005).…”

Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis

Humphreys

Chan

et al. 2006

Cell Microbiol

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SummaryMycoplasma arthritidis mitogen (MAM) is a superantigen secreted by M. arthritidis , an agent of murine arthritis and toxicity. We previously demonstrated that C3H mouse sub-strains differing in expression of Tolllike receptor 4 (TLR4), differed in immune reactivity to MAM due to differential engagement of TLR2 and TLR4. Here we examine the role of B7 co-stimulatory molecules in immune outcome and disease manifestations resulting from these different MAM/TLR2 and MAM/TLR4 interactions. Injections of MAM into C3H/ HeJ mice upregulated expression of B7-1 but not B7-2 on peritoneal adherent cells, whereas B7-1 expression was lower on cells from C3H/HeSnJ mice. Anti-B7-1 antibody but not anti-B7-2, injected in vivo , changed the type 1 cytokines in MAM-injected C3H/ HeJ mice to a type 2 cytokines and, conversely, the type 2 response in C3H/HeSnJ mice injected with anti-B7-1 shifted to a type 1 pattern. Whereas anti-B7-2 exerted no effect on disease in either mouse strain, anti-B7-1 significantly delayed the lethal toxicity of M. arthritidis in C3H/HeJ mice but enhanced arthritis in C3H/HeSnJ mice. Thus, TLR-mediated regulation of B7-1 results in diverse cytokine profiles in C3H substrains, and that the interaction of MAM with different TLR(s) may differentially affect cytokine responses and ultimately, M. arthritidis disease.

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Mycoplasma arthritidis Pathogenicity: Membranes, MAM, and MAV1

Cited by 6 publications

References 70 publications

Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components fromMycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2

Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components fromMycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2

Genome of Mycoplasma arthritidis

TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis

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