| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Porphyromonas gingivalis, a gram-negative, obligatery anaerobic rod, is one of the periodontopathogenic bacteria. P.gingivalis has two multidrug (xenobiotic) transporters belonging to the resistance-nodulation-cell division (RND) family, which was found by BLAST search for open reading fames homologous to the AcrAB-TolC efflux pump of Escherichia coli in die P.gingivalis W83 genome (TIGR). One of them, designated as Xep (for xenobiotic exporter of Porphyromonas) CAB. Pumps out various kinds of structurally-unrelated drugs (acriflavine, puromycin, sodium dodecyl sulfate, norfloxacin, minocycline etc.) in P.gingivalis cells, because the mutants in which these genes had been disrupted by the insertion of a drug-resistant cassette were more sensitive to various drugs, and accumulated a larger amount of acriflavine inside the cell, than the parent strain, ATCC33277. The active efflux depends upon an electrochemical potential of proton because the amount of acriflavine accumulated in the cel
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ls of the parent and mutant strains increased by the addition of a proton conductor (CCCP) to the same extent. It is suggested that XepCAB also exports silver ions. This is the first report for the RND-type multidrug exporter of obligate anaerobes. These results suggest that multidrug-resistant variants of P.gingivalis, e.g. with the overexpression of the pump, may appear in the future. It is assumed by computer analysis on the P.gingivalis genome that this bacterium has six two-component regulatory systems. Among them, fimS/fimR and gppX mutations had no effect on the resistance against the drugs and heavy metal ions examined, which indicates that the expression of xepCAB is not regulated by these two-component systems. Two of the MATE (multidrug and toxic coumpound extrusion)-type pumps of P.gingivalis (PG1117 and PG0636) did not export any drugs and metal ions examined. MC-207,110, an inhibitor for RND-type exporters of Pseuclomonas aeniginosa, seems to inhibit the activity of XepCAB. Less
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