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Antimicrobial Agents and Chemotherapy, September 2001, p. 2609-2615, Vol. 45, No. 9
Departments of
Medicine1 and Molecular Virology and
Microbiology,4 Baylor College of Medicine and
Veterans Affairs Medical Center, Houston, Texas 77030;
Department of Endoscopy, Hokkaido University School of
Medicine, Sapporo, Japan2; and
Department of Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul,
Korea3
Received 23 January 2001/Returned for modification 30 April
2001/Accepted 23 June 2001
We previously reported that inactivation of rdxA
and/or frxA converted Helicobacter pylori
from metronidazole sensitive to metronidazole resistant. To examine the
individual roles of rdxA and frxA in the
development of metronidazole resistance in H. pylori, we
examined the status of rdxA and frxA from
12 pairs of metronidazole-sensitive and -resistant H.
pylori isolates obtained following unsuccessful therapy
containing metronidazole. Arbitrary primed fingerprinting analyses
revealed that the genotypes of 11 sensitive and resistant pairs of
strains were essentially identical. Amino acid sequence identities of
RdxA and FrxA from the 14 metronidazole-sensitive isolates ranged from
92 to 98% and 95 to 98%, respectively, compared to that of H.
pylori J99 (MIC, 1 µg/ml). All strains with high-level metronidazole resistance (MICs, 128 µg/ml) contained premature truncation of both RdxA and FrxA caused by nonsense and/or frameshift mutations. Strains with intermediate resistance to metronidazole (MICs,
32 to 64 µg/ml) contained a single premature truncation and/or
altered RdxA and FrxA caused by nonsense, frameshift, and unique
missense mutations. The low-level metronidazole-resistant strains
(MICs, 8 µg/ml) contained unique missense mutations in FrxA but no
specific changes in RdxA. The results demonstrate that alterations in
both the rdxA and frxA genes are required for moderate and high-level metronidazole resistance and that metronidazole resistance that develops during anti-H.
pylori therapy containing metronidazole is most likely to
involve a single sensitive strain infection rather than a coinfection
with a metronidazole-resistant strain.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.9.2609-2615.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
DNA Sequence Analysis of rdxA and
frxA from 12 Pairs of Metronidazole-Sensitive and
-Resistant Clinical Helicobacter pylori
Isolates
*
Corresponding author. Mailing address: Department of
Medicine, Veterans Affairs Medical Center, 2002 Holcombe Blvd., Rm.
3A-320 (111D), Houston, TX 77030. Phone: (713) 794-7801. Fax: (713)
795-4471. E-mail: dkwon{at}bcm.tmc.edu.
Antimicrobial Agents and Chemotherapy, September 2001, p. 2609-2615, Vol. 45, No. 9
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.9.2609-2615.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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