Generation of drug-resistant mutants of Helicobacter pylori in the presence of peroxynitrite, a derivative of nitric oxide, at pathophysiological concentration

In the present study it has been shown that the reactive nitrogen species, peroxynitrite, can cause at least a 7.1-fold increase in the frequency of occurrence of drug-resistant mutants of Helicobacter pylori at a pathophysiological concentration (e.g. 1.0 mu M) and in the presence of CLR. Furthermore, the CLR MIC of these resistant H. pylori strains increased by at least 250 times or higher in CLR susceptibility. In the 45 resistant strains, the modification of 23S rRNA A2142G was the predominant mutation (22/45), followed by A2143G (17/45) within the sequences of 23S rRNA. The other mutants were one each (1/45) in A2142T, and T2269G, and two each (2/45) in C2695G and T1944C, respectively. These results show that the inflammatory host reaction involving induction of reactive oxygen species (e.g. O-2(.-)), and the inducible form of nitric oxide synthase, is a significant cause of mutation via peroxynitrite formation, particularly in drug-resistant bacterial strains.