Research

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 (Keilberg et al. 2016). Multiple input signals are sensed by H. pylori to orient itself inside the stomach, including pH, urea, reactive oxygen species, arginine, fumarate, cysteine, and autoinducer 2, but a particularly important one is lactate that was discovered as part of a collaboration with the lab of Anne Roujeinikova (Machuca et al. 2017).  L-lactate is used as a major nutrient by H. pylori (Keilberg et al. 2021) and also  to activate a response that allows H. pylori to resist complement (Hu and Ottemann, 2023). Indeed, a role for complement in lower H. pylori infection was not entirely known before the lacate discovery. 

Our lab has made substantial contributions to our understanding of how flagella are used and operate in two areas. The first was a finding that H. pylori does not turn off flagella synthesis when making a biofilm and instead incorporates the flagellar filament as a key part of the biofilm matrix (Hathroubi et al. 2018). The second has been in the area of differences in the flagellar proteins building on seminal work from the Jensen and Liu labs that found flagellar motors are highly variable between different bacterial species. H. pylori has the largest known motor, able to incorporate 18 MotAB stator units (E. coli has only 12), and additionally incorporate many other proteins that have only recently been identified. Our lab played key roles in identifying these H. pylori flagellar proteins. For example, we characerized the first flagellar C-ring with four types of proteins instead of the usual three, finding that all four are needed for motility (Lowenthal et al. 2009). We then worked on the location and function of FliL, a widely conserved flagellar protein (Liu et al. 2023; Tachiyama et al. 2022). In Sagoo et al. 2024 and Liu et al. 2024, we described the components that make up a structure called the flagellar cage. This structure had been seen on electron tomography, but its identity and function were entirely unknown. Our lab identified the cage proteins as remote homologs of the type 4 pili proteins PilMNO. These proteins create the lower cage that encircles the MotAB stator. Surprisingly, loss of these proteins resulted in H. pylori that migrate better on soft agar, instead of operating as predicted to enhance motility. We determined that these proteins inhibited soft agar migration because they drive H. pylori to form aggregates, through an as-yet-unknown mechanism. 

Description to come!