UC Santa Cruz

Helicobacter pylori is a human stomach pathogen and class 1 carcinogen responsible for the development of peptic ulcers and gastric cancer. H. pylori infects around half of the global population and is a high priority target for the development of new eradication therapies by the WHO. Exploring alternative treatment options for H. pylori is imperative with increasing failure rates for antibiotic treatment. Here we explore the influence of factors that affect antibiotic efficacy at both the therapeutic and bacterial resistance mechanism levels. In the first study, we explore the effect of the proton pump inhibitor omeprazole on the growth and redistribution of H. pylori strain SS1 in murine gastric glands. Using the bacterial localization in gastric glands (BLIG) method to enumerate intraglandular H. pylori populations, we find that omeprazole promotes the growth and redistribution of bacterial populations in gastric glands in mice. We also find that this effect is dose- and region-dependent. Lower doses of omeprazole promote growth and redistribution as a measure of gland population and gland occupancy in both the gastric antrum and gastric corpus, while higher doses of omeprazole diminish growth and redistribution. We also find that the intraglandular population of H. pylori grows and redistributes in the gastric antrum more robustly than observed in the gastric corpus. Taken together, these results indicate that omeprazole influences gland-resident populations of H. pylori in previously unreported ways. Our second study partially characterizes a putative efflux pump discovered during an RNAseq screen of biofilm-forming H. pylori. Using Phyre2 and the NCBI database, we found that the putative efflux pump, HP0759, was most similar to NorM-like efflux pumps. We also report that an HP0759 knockout is more susceptible to rifampicin, but not other antibiotics, as measured by E-test. Both studies present new findings on alternative mechanisms of drug response and survival in the stomach by H. pylori.