Research
Image from review article Keilberg & Ottemann (2016). Environ Microbiol 18, 791.
Background
The Ottemann lab studies the stomach-infecting bacterium, Helicobacter pylori (H. pylori). H. pylori infects about 50% of the global population, a whopping 3.9 billion people. It is most prevalent in the developing world, but even in the United States, it colonizes 35% of the population. In these individuals, H. pylori triggers chronic inflammation and it spurs disease—ulcers and cancer—in ~15% of them. Ulcers are non-healing wounds in the stomach lining that cause significant morbidity and some mortality. H. pylori is responsible for 90% of ulcers, causing this disease in ~20 million people annually. Gastric cancer is in the top five leading cause of cancer deaths, killing over 750,000 people annually, with H. pylori responsible for ~90% of gastric cancer cases. While the recent incidence of H. pylori infection has declined in the high-income countries but still remains in 10-20% of the population. H. pylori infections can be eliminated by antibiotics, which in turn cure ulcers and prevent gastric cancer. Indeed, gastric cancer is considered one of the most preventable cancers because we know the cause. H. pylori infections, unfortunately, can be difficult to eradicate: Standard therapy fails in about 25% of cases. Improving H. pylori cures is a top health priority and our lab is focused on this goal by identifying new targets for therapeutics.
One attribute that H. pylori uses to colonize the stomach is flagellar motility and chemotaxis. Chemotaxis is the process by which bacteria sense environmental cues and move in response. The Ottemann lab has a particular expertise in understanding how chemotaxis and motility foster bacterial disease. We are currently exploring three main themes: (1) What chemotaxis signals are sensed by H. pylori and what benefits do these confer? (2) How are flagella regulated and used by H. pylori? (3) What growth forms does H. pylori adopt during acute and chronic infection?
H. pylori and it's chemotaxis signals that it moves toward (green) and away (red). Adapted from Keilberg and Ottemann, 2016,
Chemotaxis signals reveal conditions H. pylori "cares" about
Chemotaxis is system in which bacteria use specific receptor proteins to sense signals and then swim in response, toward beneficial compounds and away from harmful ones. H. pylori possesses four chemoreceptors called TlpA, TlpB, TlpC and TlpD. Each of the chemoreceptors senses distinct input signals, and transfers the information via a signal transduction system that in turn regulates swimming. Our lab has defined that chemotaxis promotes initial colonization and attainment of high bacterial numbers, spread to new parts of the stomach, and triggering a host response that leads to inflammation. We are currently working on diverse projectsto find signals that are sensed inside the stomach, the role of the distinct chemoreceptors, when and where chemotaxis is used in the stomach, and the molecular details of chemotaxis protein function. Multiple input signals are sensed by H. pylori to orient itself inside the stomach, including pH, urea, reactive oxygen species, arginine, fumarate, cysteine, lactate, and autoinducer 2. More description to come!
H. pylori uses flagella to modulate a variety of behaviors
Description to come!
H. pylori grows rapidly during early infection then slows for the long-term
Description to come!