Analysis of the cytotoxicity of virulent Mycobacterium tuberculosis to human fibroblast cells

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We have previously reported that virulent Mycobacterium tuberculosis exhibits cytotoxicty to human embryonic lung fibroblast cell line (J. Interferon Cytokine Res., 2001, Antimicrob. Agents Chemother., 2002, 2005). The bacterial cytotoxicity correlates their virulence which is reported. In order to investigate the mechanisms of the cytotoxicity, biomedical and immunological character we investigate that the inducing activity of nitric oxide (NO) from human lung cell line A549 and the susceptibility to NO using twelve BCG strains. Among them three strains, Phipps, Russia and Japan, were observed inducing NO production from A549 higher than others. These strains are close to genetic background and exhibited synergistic effect of IL-1 and TNF-α on the NO production. Therefore, these strains may keep original characters of the primarily BCG vaccine and still have protective activity against Mycobacterium tuberculosis. On the other hand, in order to investigate the susceptibility to growth … More inhibitory or toxic effect of NO on bacteria, the twelve strains were cultured with Middlebrook 7H9 broth containing 10 % ADC and (0 to 1 mM) NaNO_2 for 21 days. Three BCG strains, Brazil, Glaxo and Russia, were very sensitive to NO, however, others were tolerant. The character to the susceptibility to NO did not correlate to the genetic background of BCG strains. NO tolerant strains may play a role in the survival in host and these strains could be useful for carrier of recombinant BCG vaccine in future.A series of sugar derivatives were synthesized from stachyose, a sugar compound of Stachys sieboldi Miq, and evaluated for antibacterial activity against Mycobacterium tuberculosis, Mycobacterium avium, and Staphylococcus aureus, and their structure-activity relationships were studied. The results showed that the compound OCT359 (allyl O-(2,3,4,6-tetra-O-acetyl-α -Dgalactopyranosyl)-(1->6)-O-(2,3,4-tri-O-acetyl-a-D-galactopyranosyl)-(1->6)-0-2,3,4-tri-O-acetyl-β-D-glucopyranoside) exhibited in vitro antibacterial activity. The allyl group at C-1 and the acetoxy groups of the manniotrioside were requisite for the antibacterial activity. Less