Master of Science
Microbiology and Immunology
Helicobacter pylori (HP) affects 50% of the population and 1-10% of infections lead to gastric ulcers. HP utilizes virulence factors like urease activity, CagA to induce IL8 secretion from gastric cells, and flagella for motility. Mounting antibiotic resistance of HP necessitates new treatments. Lactic acid bacteria (LAB) secretions have anti-HP activity effects. Sensor kinases (SKs) sense small molecules and initiate downstream signaling cascades and the SKs HP0165 and HP0244 control the urease response and motility. They are thus potentially involved in mediating the responses to LAB secretions. We show the role of the HP SKs in the LAB supernatant context using knockout mutant studies and RNA-Seq on gastric cells infected with LAB-treated HP and work towards identifying the active molecules the SKs sense via metabolomics and quantitative proteomics. This work may lead to a novel treatment of HP as an alternative to antibiotics.
Summary for Lay Audience
H. pylori (HP) presents a global threat to human health that requires new methods of treatment as prevalent HP strains can resist current medications. Probiotics are an alternative method of treatment and have been used to treat other pathogens of concern and HP itself. One group that falls under the probiotic umbrella are lactic acid bacteria (LABs) that have been studied for their anti-bacterial effects. Previous work in our laboratory finds that molecules secreted by these LABs affect HP’s growth, acid resistance, and pro-inflammatory properties. These molecules are an easily administered treatment alternative to live bacteria that may be used on their own to treat HP infection or as an additive to current medications. The work presented in this thesis first identifies the role of bacterial sensors in sensing these molecules in a mouse-associated strain of HP. This thesis also illuminates which gastric genes are affected upon exposure to HP treated with these molecules using studies on cultured gastric cell RNA isolated after infection with treated-HP. We found that the activity of specific human genes related to inflammation was decreased by molecule treatment compared to a control in which there was no LAB molecules. Further, the LAB secretions containing these molecules were analyzed independently to determine the composition of small molecules from different LAB strains. We narrowed down the identity of the active molecules to 35 candidates and we find that organic acids and compounds with previously characterized antibacterial activity were present in most samples. Thus, these active molecules will be individually tested against HP and may one day lead to the production of a novel over-the-counter medication comprised of a mixture of these molecules to combat HP infections.
Carroll, Daelyn, "Mechanisms of lactic acid bacteria secretions as anti-Helicobacter pylori agents" (2023). Electronic Thesis and Dissertation Repository. 9232.
Available for download on Thursday, May 01, 2025