1 research outputs found
Role of the rdxA and frxA genes in oxygen-dependent metronidazole resistance of Helicobacter pylori
Almost 50 % of all Helicobacter pylori isolates are resistant to
metronidazole, which reduces the efficacy of metronidazole-containing
regimens, but does not make them completely ineffective. This discrepancy
between in vitro metronidazole resistance and treatment outcome may
partially be explained by changes in oxygen pressure in the gastric
environment, as metronidazole-resistant (MtzR) H. pylori isolates become
metronidazole-susceptible (MtzS) under low oxygen conditions in vitro. In
H. pylori the rdxA and frxA genes encode reductases which are required for
the activation of metronidazole, and inactivation of these genes results
in metronidazole resistance. Here the role of inactivating mutations in
these genes on the reversibility of metronidazole resistance under low
oxygen conditions is established. Clinical H. pylori isolates containing
mutations resulting in a truncated RdxA and/or FrxA protein were selected
and incubated under anaerobic conditions, and the effect of these
conditions on the MICs of metronidazole, amoxycillin, clarithromycin and
tetracycline, and cell viability were determined. While anaerobiosis had
no effect on amoxycillin, clarithromycin and tetracycline resistance, all
isolates lost their metronidazole resistance when cultured under anaerobic
conditions. This loss of metronidazole resistance also occurred in the
presence of the protein synthesis inhibitor chloramphenicol. Thus,
factor(s) that activate metronidazole under low oxygen tension are not
specifically induced by low oxygen conditions, but are already present
under microaerophilic conditions. As there were no significant differences
in cell viability between the clinical isolates, it is likely that neither
the rdxA nor the frxA gene participates in the reversibility of
metronidazole resistance