Molekularna analiza gena nim i inducibilne rezistencije na metronidazol u kliničkih izolata grupe Bacteroides fragilis [Molecular analysis of nim genes and inducible metronidazole resistance in Bacteroides fragilis clinical isolates]

Abstract

The study is essentially based on detection of nim genes in B. fragilis group strains, in vitro induction of resistance to metronidazole in strains which are phenotypically sensitive to metronidazole and measurement of LDH activity in strains with induced resistance to metronidazole. All strains were nim-gene negative, as well as sensitive to metronidazole. In-vitro induction of metronidazole resistance is selected in nim-negative strains, after repeated exposure to subinhibitory concentrations of metronidazole incorporated into growth medium. The MIC values for metronidazole of the induced strains ranged from 8 to 96 mg/L. Only one B. fragilis strain with induced resistance to metronidazole demonstrated an emergent increase in LDH activity. We believe that genetic mutations were responsible for the increased activity. A significant decrease in LDH activity of the most other strains was contrary to previous findings in which, underlying higher metronidazole MICs, an increase in LDH activity compensated for the decreased activity of PFOR complex. These findings could be explained if the induction caused only physiologic and not genetic changes. These results provide the first insights into the mechanisms of metronidazole resistance during the exposure of nim-negative strains to antibiotic, that have been observed, but not investigated in detail, by other authors