- About CURE
Elizabeth Marcus, MD
Clinical Instructor, Department of Pediatrics, David Geffen School of Medicine at UCLA
The research interest of Dr. Marcus is in the area of Helicobacter pylori-induced gastritis and the influence of the gastric microenvironment on the physiology of this microorganism. H. pylori is a gram negative bacteria that infects the normal acid secreting human stomach leading to gastritis, gastric and duodenal ulcer disease, and gastric cancer. The in vitro bioenergetic profile of H. pylori is that of a neutralophile. In the absence of urea, H. pylori grows maximally at pH 7.4. However, in the presence of physiologic urea concentrations in unbuffered medium, this gastric pathogen requires a pH of 3.5 or less for growth and survival, to avoid elevation of medium pH to lethal levels. Although controversial, the pH at the gastric surface, the site of H. pylori colonization, is most likely ~pH 3.0 for most of the 24 hr period, as determined by pH electrodes, fluorescent dye probes and in vivo transcriptomics. Traditionally, studies of the H. pylori acid stress response have been performed by growing the organism at neutral pH followed by exposure to low pH. However, this is the reverse of the in vivo condition, where the organism is exposed to low pH with excursions to slightly less acidity during the digestive phase after food intake. The aim of Dr. Marcus' project is to determine the effects of mimicking the in vivo pH conditions using a novel in vitro growth system, allowing for sustained exposure to acidity and urea. Effects of exposure to chronic acidty on survival, morphology, gene and protein expression, and enzyme activity will be determined. During the initial funding period, one significant finding was that genes involved with cell wall synthesis and cell division were downregulated with chronic acid exposure, which, in agreement with obtained survival and microscopy data, suggests that the bacteria are not dividing at more extreme acidity. Susceptibility to ampicillin was only present at higher pHs, best at pH 7.4 This finding led to the development of a second aim to test the utility of dual therapy with amoxicillin and strong acid suppression in a gerbil model. Dr. Marcus is a CURE Pilot and Feasibility recipient.