Research

Image from review article by lab member Daniela Keilberg: Keilberg & Ottemann (2016). Environ Microbiol 18, 791.

Background

Some bacteria are skilled: they can stay put inside the gastrointestinal tract for a person’s lifetime despite numerous removal efforts, including constant flow of food and mucus, and a robust immune response. Our lab seeks to understand what it takes for a bacterium to survive and thrive in such a highly challenging environment, the human stomach. Many bacteria that are helpful and harmful--such as members of the microbiota and pathogens like Helicobacter pylori--are capable of this so-called chronic colonization, but we do not yet understand what abilities bacteria need to promote a life long human association.

Studies

The Ottemann lab studies chronic colonization in the bacterium Helicobacter pylori. This bacterium colonizes about 50% of the world’s population. People acquire H. pylori infections as children, and the bacteria typically remain with them for their lifetimes. H. pylori colonization can result in a variety of host outcomes. In some people, H. pylori infection causes severe disease including gastric and duodenal ulcers and gastric cancer. In other people, the infection causes an asymptomatic inflammation. In yet others, the infection can trigger a type of immune response that protects people from allergic disease such as asthma and inflammatory bowel diseases. For all of these outcomes, H. pylori must first establish a chronic infection.

In the Ottemann lab we focus on how H. pylori senses and responds to its stomach environment, with a particular focus on a process called chemotaxis and flagellar motility. 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.

Groundwork

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. We are looking to understand how these input signals are sensed and why H. pylori responds to them. f Image from review article by lab member Daniela Keilberg: Keilberg & Ottemann 2016. Environ Microbiol 18, 791.

Chemoreceptors bind ligands and control signaling of the chemotaxis protein complex to regulate flagellar rotation. We strive to understand how each chemoreceptor is involved in the signal input, how the various coupling proteins CheW and CheV are involved in the signal transfer, and how other proteins such as CheZ and ChePEP modulate the chemotaxis response. Image from a review article by lab member Kieran Collins: Collins et al. 2014. Microbiol Mol Biol Rev 78:672.

Flagella can serve multiple functions, including to make the biofilm matrix mesh, presumably when not rotating. Below are images of the H. pylori biofilm state as described in Hathroubi, S., Hu, S. & Ottemann, K. M. (2020). Genetic requirements and transcriptomics of Helicobacter pylori biofilm formation on abiotic and biotic surfaces. NPJ Biofilms Microbiomes 6, 56.