Antibiotic resistance in Helicobacter pylori (H. pylori) is a growing problem, with failure rates for the standard treatment now around 70%. The bacterium exhibits a high mutation rate and evolves rapidly. Antibiotic resistance does not require uptake of antibiotic resistant genes in H. pylori. Instead, it is associated with simple point of mutations, and a variety of single nucleotide polymorphisms (SNPs) can lead to the same outcome. In H. pylori, the most frequent mutations associated with clarithromycin resistance are the transitions A2143G and A2142G in 23S rRNA. Mutational inactivation of electron carriers: rdxA and frxA genes through frameshift mutations cause the acquisition of metronidazole resistance. In contrast amino acid substitutions through point mutations in the rpoB gene at codons, 149, 524 to 545 and 586 relate to rifabutin resistance. However, the published mutations only explain about 80% of antibiotic resistance in H. pylori and also fail to explain the step-wise progression in resistance strength observed. We conducted antibiotic resistance induction experiments. We induced resistance to five different antibiotics (Clarithromycin, Metronidazole, Tetracycline , Rifabutin and Ciprofloxacin) in the wild-type strain (sensitive to all antibiotics). We progressed from low to high antibiotic concentrations, and compared the genomes of the mutant isolates, wild-type strains and other reference strains via genome sequencing technology in order to identify new SNPs. Preliminary study identified two new mutations in the genes associated with metronidazole and rifampicin resistance. However the mutations were also present in the wild-type strains, showing that they were not related to resistance. In addition, substitution of amino acids at codon 91 in the target gene associated with ciprofloxacin resistance, was identified. Study replication and further analysis will be performed. Ultimately, this study will improve understanding of the genetic mechanisms underlying the growing problem of antibiotic resistance. The findings may translate into improved policy on the optimal use of eradication therapies, so as to limit the spread of resistance.