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. 2003 Oct;62(10):976–982. doi: 10.1136/ard.62.10.976

Role of peptidoglycan subtypes in the pathogenesis of bacterial cell wall arthritis

E Simelyte 1, M Rimpilainen 1, X Zhang 1, P Toivanen 1
PMCID: PMC1754332  PMID: 12972477

Abstract

Background: Bacterial cell wall (CW) arthritis develops in susceptible strains of rats after a single intraperitoneal injection of the CW from certain bacterial species, both pathogenic and non-pathogenic. For the development of chronic bacterial CW arthritis, the structure of the bacterial peptidoglycan (PG) has been found to be decisive.

Objective: To define the role of PG subtypes in the pathogenesis of chronic bacterial CW arthritis.

Method: Arthritis was induced with CWs of Lactobacillus plantarum, L casei B, L casei C, and L fermentum. Gas chromatography-mass spectrometry was used to measure the presence of CW derived muramic acid in the liver and to determine PG subtypes. CWs were also tested for their resistance to lysozyme in vitro.

Results: These results and those published previously indicate that PGs of CWs which induce chronic arthritis, no matter whether they were derived from strains of Streptococcus, Bifidobacterium, Collinsella, or Lactobacillus, all have lysine as the third amino acid of the PG stem peptide, representing PG subtypes A3α and A4α. Those strains which induce only transient acute arthritis or no arthritis at all do not have lysine in this position, resulting in different PG subtypes.

Conclusions: In vivo degradation of only those PGs with the subtypes A3α and A4α leads to the occurrence of large CW fragments, which persist in tissue and have good proinflammatory ability. CWs with other PG subtypes, even if they are lysozyme resistant, do not cause chronic arthritis, because the released fragments are not phlogistic. It is emphasised that a variety of microbial components not causing inflammation have been found in animal and human synovial tissue.

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Figure 1.

Figure 1

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PG structures in the Lactobacillus strains used. The L plantarum belongs to the D-glutamine-m-diaminopimelic acid-D-alanine subtype (A1γ), the two L casei share the L-lysine-D-asparagine subtype (A4α), whereas L fermentum has the subtype L-ornithine-D-asparagine (A4ß). The enzymes degrading PG cleave specific bonds: lysozyme (ß-N-acetylglucosaminidase) and N-acetylmuramyl-L-alanine-amidase.

Figure 2.

Figure 2

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Development of arthritis in rats injected IP with Lactobacillus CW. The injection dose was 24 mg of CW dry weight/100 g of rat body weight for L plantarum ATCC 4008 or L casei C ATCC 25302, and 8 mg for L casei B ATCC 11578 or L fermentum ATCC 14931. The arthritis score is calculated as a mean value (SEM) for the number of rats indicated at the top. Rats which died on day 2 are excluded from this figure.

Figure 3.

Figure 3

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Muramic acid content in rat liver analysed by GC-MS. On day 0 rats were injected IP with CW from L plantarum ATCC 4008, L casei C ATCC 25302, L casei B ATCC 11578, or L fermentum ATCC 14931. The muramic acid levels are given as the mean value (SEM) for four to six rats. Asterisks indicate significant differences (p<0.05) when the rats injected with L plantarum, L casei C or L casei B CWs were compared with those injected with L fermentum CW. Significance is shown separately for each day of analysis.

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