| Summary: | Includes abstract. === Includes bibliographical leaves (leaves 89-101). === Bacteroides fragilis is a gut commensal in both humans and animals where it benefits the host through metabolizing indigestible compounds, stimulating the immune system and protecting against pathogen colonization. However, it is also an opportunistic pathogen, responsible for approximately half of anaerobic bacteraemias. Metronidazole is used to treat anaerobic infections. It diffuses into the celI as an inactive prodrug where it is reduced to form nitro anion and nitroso and hydroxylamine radicals. These chemically reactive compounds interact with DNA causing strand breaks and base mutations; the damage accumulates and leads to cell death. Mechanisms of metronidazole resistance in B. fragilis include decreased activity of oxidation/reduction enzymes, over-expression of multidrug efflux pumps and the conversion of metronidazole to non-toxic derivatives by nitroimidazole nitroreductases (encoded by nim genes). However, metronidazole resistance could also potentialIy be mediated by the over-expression or enhanced activity of DNA repair proteins. Thus, DNA repair in B. fragilis should be thoroughly investigated.
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