Open AccessFrame‐shift mutations in NAD(P)H flavin oxidoreductase encoding gene ( frxA ) from metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in metronidazole resistance
Author(s) -
Kwon Dong H,
Kato Mototsugu,
ElZaatari Fouad A.K,
Osato Michael S,
Graham David Y
Publication year - 2000
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.2000.tb09193.x
Subject(s) - metronidazole , helicobacter pylori , microbiology and biotechnology , biology , nitroreductase , nad+ kinase , gene , genetics , antibiotics , biochemistry , enzyme
Metronidazole is a critical ingredient for combination therapies of Helicobacter pylori infection, the major cause of peptic ulcer and gastric cancer. It has been recently reported that metronidazole resistance from H. pylori ATCC43504 is caused by the insertion of a mini‐IS605 sequence and deletion of sequences in an oxygen insensitive NAD(P)H nitroreductase encoding gene ( rdxA ). We also found that an additional gene ( frxA ) encoding NAD(P)H flavin oxidoreductase in the same strain was truncated by frame‐shift mutations. To assess whether the frxA truncation is also involved in metronidazole resistance, metronidazole sensitive H. pylori strains ATCC43629 and SS1 were transformed by the truncated frxA gene cloned from strain ATCC43504. All transformed cells grew on agar plates containing 16 μg ml −1 of metronidazole. The involvement of the frxA gene in metronidazole resistance was also confirmed by insertion inactivation of frxA and/or rdxA genes from strain ATCC43629 and one metronidazole sensitive clinical isolate H. pylori 2600. In addition, the frxA gene cloned from the H. pylori 2600 showed metronidazole nitroreductase activity in Escherichia coli and rendered ordinary metronidazole resistant E. coli to metronidazole sensitive cell. These results indicate that the frxA gene may also be involved in metronidazole resistance among clinical H. pylori isolates.