, 1987; Smalley et al., 1998a, b), and μ-oxo bisheme is more active in destroying H2O2 in the presence of monomeric hemin (Jones et al., 1973). As the functional hydroxamic acid groups of DFO are coordinated to the iron of hemin in physiological pH (Baysal et al., 1990), both of the monomeric and dimeric hemins present in the neutral pH medium used in this study may react with
Everolimus research buy DFO, and hence catalytic degradation of H2O2 by μ-oxo bisheme may have decreased in the presence of DFO, enhancing the killing effect of H2O2 against P. gingivalis. Among the antimicrobials used for the treatment of periodontitis, metronidazole is particularly suitable due to its limited side effects and its restricted spectrum of activity against obligate anaerobes (Sato et al., 2008). Metronidazole exerts its effect only when it is partially reduced by reacting with ferredoxin (in reduced form), and because this reduction usually happens
Idasanutlin in vitro only in anaerobic cells, the drug has relatively little effect upon human cells or aerobic bacteria (Lockerby et al., 1984; Narikawa et al., 1991). In the present study, the antibacterial effect of metronidazole against P. gingivalis W83 was enhanced by DFO while that of the other antibiotics tested was not affected by DFO. It is noteworthy that the expression of pyruvate : ferredoxin oxido-reductase, which has an essential role in the generation of reduced ferredoxin in
P. gingivalis, is up-regulated under hemin-limiting conditions (Dashper et al., 2009). It is conceivable therefore that the increased effect of metronidazole on P. gingivalis in the presence of DFO may be due to the enhancement of the reaction between metronidazole and the reduced ferredoxin as a result of iron/hemin deprivation by DFO. Synergy between iron-chelators and antibiotics such as gentamicin, chloramphenicol and cephalosporin class has been observed in several siderophore-producing bacteria (van Asbeck et al., Tolmetin 1983a, b; Hartzen et al., 1991, 1994). It was proposed that when protein synthesis or cell wall synthesis is decreased by antimicrobial agents, the production or transport of siderophores through the cell wall is affected and the microorganisms becomes more sensitive to iron deprivation (van Asbeck et al., 1983a, b). In P. gingivalis which lacks siderophore, a disturbance in protein and cell wall synthesis by antibiotics such as tetracycline and ampicillin may not aggravate the situation of DFO-induced iron/hemin limitation unlike in siderophore-producing bacteria. In periodontal pockets, microorganisms are organized in biofilms and it is known that subgingival bacteria in biofilms are more resistant to antimicrobial treatment (Darveau et al., 1997).