Publications
2023
The Complement System is present in the stomach and challenges H. pylori, which survives by preventing complement proteins from attaching to its surface. Such a resistance mechanism has not been seen previously.
Shuai Hu (PhD 2022) determined that H. pylori uses L-lactate to mount a complement resistance phenotype. Complement is a potent antimicrobial in the stomach, lowering colonization by 100-fold. H. pylori overcomes this barrier not by halting complement activation, but by removing the complement protein C4b from its surface. Hu S, Ottemann KM. Helicobacter pylori initiates successful gastric colonization by utilizing L-lactate to promote complement resistance. Nat Commun. 2023 Mar 27;14(1):1695. doi: 10.1038/s41467-023-37160-1.
fliL mutants are non-motile if they retain the N-terminal region, but close to normal if the full gene is deleted.
Previous phenotypes ascribed to loss of the FliL flagellar protein varied from non-motile to normal motile. Xiaolin Liu (visiting student, now postdoc), in work with collaborate Anna Roujeinikova, determined a key correlate of this variability: whether the mutant design retained a substantial chunk of the FliL N terminus. This correlate heald true across multiple bacterial species. Liu X, Roujeinikova A, Ottemann KM. FliL Functions in Diverse Microbes to Negatively Modulate Motor Output via Its N-Terminal Region. mBio. 2023 Apr 25;14(2):e0028323. doi: 10.1128/mbio.00283-23.
H. pylori chronic inflammation fluctuates in a manner that can vary between WT and mutants.
Kevin Johnson (PhD 2021) found that H. pylori inflammation climbs but then does not hold steady, it fluctuates. The magnitude and timing of peaks varied between WT and a tlpA mutant, which also colonized to higher levels in early infection. Johnson KS, ... Ottemann KM et al. Helicobacter pylori Chronic-Stage Inflammation Undergoes Fluctuations That Are Altered in tlpA Mutants. Infect Immun. 2023 Jan 24;91(1):e0032222. doi: 10.1128/iai.00322-22.
2022
All gastric Helicobacter species lack the chemotaxis methylation adaptation enzymes CheR and CheB
Xiaolin Liu (visiting student, now postdoc) found that gastric Helicobacter spp. lack the chemoreceptor methylase CheR and the methylesterase CheB, which allow adaptation and migration across a wide range of chemical concentations. All enterohepatic Helicobacter retain them. The correlation is so strong as to be predictive of colonization location, and suggests the surprising idea that adaptation is not needed in some niches. Liu X, Ottemann KM. Methylation-Independent Chemotaxis Systems Are the Norm for Gastric-Colonizing Helicobacter Species. J Bacteriol. 2022 Sep 20;204(9):e0023122.
FliL forms a lovely ring of rings at the flagellar stator
In collaborative work with the labs of Anna Roujeinikov and Jun Liu, we reported the localization and structure of FliL in the H. pylori flagellar motor. Tachiyama S, et al.. The flagellar motor protein FliL forms a scaffold of circumferentially positioned rings required for stator activation. Proc Natl Acad Sci U S A. 2022 119(4):e2118401119. doi: 10.1073/pnas.2118401119.
2021
The TlpA chemoreceptor binds three attractant ligands and one agonist ligand
Graduate student Kevin Johnson lead our collaboration with Basam Elgamoudi and the team of Victoria Korolik to identify new ligands of the TlpA chemoreceptor, which is important for colonization and inflammation control. They report two new direct binding chemoattractants, fumarate and cysteine, and also found a direct binding antagonist ligand: glucosamine. Johnson KS, Elgamoudi BA, Jen FE, Day CJ, Sweeney EG, Pryce ML, Guillemin K, Haselhorst T, Korolik V, Ottemann KM. The dCache Chemoreceptor TlpA of Helicobacter pylori Binds Multiple Attractant and Antagonistic Ligands via Distinct Sites. mBio. 2021 Aug 31;12(4):e0181921. doi: 10.1128/mBio.01819-21. Epub 2021 Aug 3. PMID: 34340539; PMCID: PMC8406319.
H. pylori infection leads to loss of specific metabolites, including lactate and members of the TCA cycle
Work done by postdoc Daniela Keilberg as a collaboration with the lab of Yana Zavros showed that H. pylori leads to loss of specific metabolites in organoids and during mouse infection. Keilberg D, Steele N, Fan S, Yang C, Zavros Y, Ottemann KM. Gastric Metabolomics Detects Helicobacter pylori Correlated Loss of Numerous Metabolites in Both the Corpus and Antrum. Infect Immun. 2021 Jan 19;89(2):e00690-20. doi: 10.1128/IAI.00690-20. PMID: 33168589; PMCID: PMC7822133.
2020
H. pylori biofilm growth requires specific genes and has defined transcriptional profile
Postdoc Skander Hathroubi and graduate student Shuai Hu found that the H. pylori G27 forms gorgeous biofilms on cell surfaces that require flagella and several interesting metabolic genes. Hathroubi S, Hu S, Ottemann KM. Genetic requirements and transcriptomics of Helicobacter pylori biofilm formation on abiotic and biotic surfaces. NPJ Biofilms Microbiomes. 2020 Nov 27;6(1):56. doi: 10.1038/s41522-020-00167-3.
H. pylori biofilm growth mode is antibiotic tolerant
Postdoc Skander Hathroubi, undergraduate Julia Zerebinski and graduate student Aaron Clarke collaborated to show that biofilm growth confers antibiotic tolerance that is dependent on surface proteins. Hathroubi S, Zerebinski J, Clarke A, Ottemann KM. Helicobacter pylori Biofilm Confers Antibiotic Tolerance in Part via A Protein-Dependent Mechanism. Antibiotics (Basel). 2020 Jun 24;9(6):355. doi: 10.3390/antibiotics9060355. PMID: 32599828
2019
What it takes to live in a gland
Ph.D. student Christina Yang turned her literature review on how to live in a gland into a publication called Control of Bacterial Colonization in the Glands and Crypts (Current Opinion in Microbiology 47:38-44, 2019).
2018
Flagella hold it all together
Postdoc Skander Hathroubi and undergraduate student Julia Zerebinski report the exciting finding that H. pylori biofilms express large amounts of flagellar apparatus genes, and these structures appear to hold the biofilm together.
Helicobacter pylori Biofilm Involves a Multigene Stress-Biased Response, Including a Structural Role for Flagella. Skander Hathroubi, Julia Zerebinski, Karen M. Ottemann mBio Oct 2018, 9 (5) e01973-18; DOI: 10.1128/mBio.01973-18
Running the ROS Gauntlet
Ph.D. student Kieran Collins went out with a bang with his finding that ROS chemotaxis is critical for H. pylori to colonize multiple gastric glands. This work made use mutant mice lacking either epithelial-produced or immune cell produced ROS. In these strains, the defect of TlpD mutants was reversed. The current model is that multiple types of host ROS limit gland colonization and that bacteria have evolved specific mechanisms to migrate through this gauntlet to establish in the glands.
Collins, K. D., Hu, S., Grasberger, H., Kao, J. Y. & Ottemann, K. M. (2018). Chemotaxis allows bacteria to overcome host-generated reactive oxygen species that constrain gland colonization. Infect Immun 86, e00878–17 (N. E. Freitag, Ed.). http://iai.asm.org/content/86/5/e00878-17.abstract
Also covered as an article of interest: Link
Helicobacter pylori Biofilm Formation and Its Potential Role in Pathogenesis
Great review article about H. pylori biofilm written as a collaboration with the Merrell lab.
Hathroubi, S., Servetas, S. L., Windham, I., Merrell, D. S., & Ottemann, K. M. (2018). Helicobacter pylori Biofilm Formation and Its Potential Role in Pathogenesis. Microbiology and molecular biology reviews : MMBR, 82(2), e00001-18. doi:10.1128/MMBR.00001-18
Article copy here
Two Spatial Chemotaxis Assays: The Nutrient-Depleted Chemotaxis Assay and the Agarose-Plug-Bridge Assay.
Korolik V., Ottemann K.M. (2018) Two Spatial Chemotaxis Assays: The Nutrient-Depleted Chemotaxis Assay and the Agarose-Plug-Bridge Assay. In: Manson M. (eds) Bacterial Chemosensing. Methods in Molecular Biology, vol 1729. Humana Press, New York, NY
Colonization, localization, and inflammation: the roles of H. pylori chemotaxis in vivo
Johnson, K. S., & Ottemann, K. M. (2018). Colonization, localization, and inflammation: the roles of H. pylori chemotaxis in vivo. Current opinion in microbiology, 41, 51–57. doi:10.1016/j.mib.2017.11.019
Article copy here
2017
TlpC directly binds the chemoattractant lactate
The Ottemann lab collaborated with crystallographer Anna Roujeinikova's lab to identify lacatate as an H. pylori chemoattractant. The Roujeinikova lab crystallized the ligand binding domain of TlpC, and found that it had bound a lactate molecule. Ottemann Lab Ph.D. student Kevin Johnson showed that lactate is an H. pylori chemoattractant that is sensed by TlpC. TlpC is the first chemoreceptor in its family to bind a ligand in the membrane proximal CACHE domain. Lactate is a preferred food for H. pylori, so tracking it down makes sense.
Machuca, M. A., Johnson, K. S., Liu, Y. C., Steer, D. L., Ottemann, K. M. & Roujeinikova, A. (2017). Helicobacter pylori chemoreceptor TlpC mediates chemotaxis to lactate. Sci Rep 7, 14089. Nature Publishing Group. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658362/
NLRP3 Controls the Development of Gastrointestinal CD11b+ Dendritic Cells in the Steady State and during Chronic Bacterial Infection
Article copy here
Cooperation of two distinct coupling proteins creates chemosensory network connections
Abedrabbo, S., Castellon, J., Collins, K. D., Johnson, K. S., & Ottemann, K. M. (2017). Cooperation of two distinct coupling proteins creates chemosensory network connections. Proceedings of the National Academy of Sciences of the United States of America, 114(11), 2970–2975. doi:10.1073/pnas.1618227114
Article copy here
Fallacy of the Unique Genome: Sequence Diversity within Single Helicobacter pylori Strains
Draper, J. L., Hansen, L. M., Bernick, D. L., Abedrabbo, S., Underwood, J. G., Kong, N., … Ottemann, K. M. (2017). Fallacy of the Unique Genome: Sequence Diversity within Single Helicobacter pylori Strains. mBio, 8(1), e02321-16. doi:10.1128/mBio.02321-16
Article copy here
2016
Spatial and Temporal Shifts in Bacterial Biogeography and Gland Occupation during the Development of a Chronic Infection
Keilberg, D., Zavros, Y., Shepherd, B., Salama, N. R., & Ottemann, K. M. (2016). Spatial and Temporal Shifts in Bacterial Biogeography and Gland Occupation during the Development of a Chronic Infection. mBio, 7(5), e01705-16. doi:10.1128/mBio.01705-16
Article copy here
The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress
Collins, K. D., Andermann, T. M., Draper, J., Sanders, L., Williams, S. M., Araghi, C., & Ottemann, K. M. (2016). The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress. Journal of bacteriology, 198(11), 1563–1575. doi:10.1128/JB.00071-16
Article copy here
How Helicobacter pylori senses, targets and interacts with the gastric epithelium
Keilberg, D. and Ottemann, K. M. (2016), H. pylori–gastric epithelium interaction. Environ Microbiol, 18: 791-806. doi:10.1111/1462-2920.13222
Article copy here
2015
Helicobacter pylori CheZ(HP) and ChePep form a novel chemotaxis-regulatory complex distinct from the core chemotaxis signaling proteins and the flagellar motor
Lertsethtakarn, P., Howitt, M. R., Castellon, J., Amieva, M. R., & Ottemann, K. M. (2015). Helicobacter pylori CheZ(HP) and ChePep form a novel chemotaxis-regulatory complex distinct from the core chemotaxis signaling proteins and the flagellar motor. Molecular microbiology, 97(6), 1063–1078. doi:10.1111/mmi.13086
Article copy here
The use of murine-derived fundic organoids in studies of gastric physiology
Schumacher, M. A., Aihara, E., Feng, R., Engevik, A., Shroyer, N. F., Ottemann, K. M., … Zavros, Y. (2015). The use of murine-derived fundic organoids in studies of gastric physiology. The Journal of physiology, 593(8), 1809–1827. doi:10.1113/jphysiol.2014.283028
Article copy here
Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation: The use of a novel in vitro model to study epithelial response to infection
Schumacher, M. A., Feng, R., Aihara, E., Engevik, A. C., Montrose, M. H., Ottemann, K. M., & Zavros, Y. (2015). Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter, 20(1), 19–28. doi:10.1111/hel.12152
Article copy here
Internal Sense of Direction: Sensing and Signaling from Cytoplasmic Chemoreceptors
Collins, K. D., Lacal, J., & Ottemann, K. M. (2014). Internal sense of direction: sensing and signaling from cytoplasmic chemoreceptors. Microbiology and molecular biology reviews : MMBR, 78(4), 672–684. doi:10.1128/MMBR.00033-14
Article copy here
2014
Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori.
Aihara, E., Closson, C., Matthis, A. L., Schumacher, M. A., Engevik, A. C., Zavros, Y., … Montrose, M. H. (2014). Motility and chemotaxis mediate the preferential colonization of gastric injury sites by Helicobacter pylori. PLoS pathogens, 10(7), e1004275. doi:10.1371/journal.ppat.1004275
Article copy here
2013
Structural basis of FliG–FliM interaction in Helicobacter pylori
Article copy here
The Degree of Helicobacter pylori-Triggered Inflammation Is Manipulated by Preinfection Host Microbiota
Rolig, A. S., Cech, C., Ahler, E., Carter, J. E., & Ottemann, K. M. (2013). The degree of Helicobacter pylori-triggered inflammation is manipulated by preinfection host microbiota. Infection and immunity, 81(5), 1382–1389. doi:10.1128/IAI.00044-13
Article copy here
A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori chemotactic response to zinc and nickel
Sanders, L., Andermann, T. M., & Ottemann, K. M. (2013). A supplemented soft agar chemotaxis assay demonstrates the Helicobacter pylori chemotactic response to zinc and nickel. Microbiology (Reading, England), 159(Pt 1), 46–57. doi:10.1099/mic.0.062877-0
Article copy here
2012
Conserved transcriptional unit organization of the cag pathogenicity island among Helicobacter pylori strains
Ta, L. H., Hansen, L. M., Sause, W. E., Shiva, O., Millstein, A., Ottemann, K. M., … Solnick, J. V. (2012). Conserved transcriptional unit organization of the cag pathogenicity island among Helicobacter pylori strains. Frontiers in cellular and infection microbiology, 2, 46. doi:10.3389/fcimb.2012.00046
Article copy here
Helicobacter pylori requires TlpD-driven chemotaxis to proliferate in the antrum
Rolig, A. S., Shanks, J., Carter, J. E., & Ottemann, K. M. (2012). Helicobacter pylori requires TlpD-driven chemotaxis to proliferate in the antrum. Infection and immunity, 80(10), 3713–3720. doi:10.1128/IAI.00407-12
Article copy here
The Helicobacter pylori autotransporter ImaA (HP0289) modulates the immune response and contributes to host colonization
Sause, W. E., Castillo, A. R., & Ottemann, K. M. (2012). The Helicobacter pylori autotransporter ImaA (HP0289) modulates the immune response and contributes to host colonization. Infection and immunity, 80(7), 2286–2296. doi:10.1128/IAI.00312-12
Article copy here
2011
Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection
Rolig, A. S., Carter, J. E., & Ottemann, K. M. (2011). Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection. Proceedings of the National Academy of Sciences of the United States of America, 108(49), 19749–19754. doi:10.1073/pnas.1104598108
Article copy here
Motility and Chemotaxis in Campylobacter and Helicobacter
Lertsethtakarn, P., Ottemann, K. M., & Hendrixson, D. R. (2011). Motility and chemotaxis in Campylobacter and Helicobacter . Annual review of microbiology, 65, 389–410. doi:10.1146/annurev-micro-090110-102908
Article copy here
ChePep controls Helicobacter pylori Infection of the gastric glands and chemotaxis in the Epsilonproteobacteria
Howitt, M. R., Lee, J. Y., Lertsethtakarn, P., Vogelmann, R., Joubert, L. M., Ottemann, K. M., & Amieva, M. R. (2011). ChePep controls Helicobacter pylori Infection of the gastric glands and chemotaxis in the Epsilonproteobacteria. mBio, 2(4), e00098-11. doi:10.1128/mBio.00098-11
Article copy here
Identification of a chemoreceptor zinc-binding domain common to cytoplasmic bacterial chemoreceptors
Draper, J., Karplus, K., & Ottemann, K. M. (2011). Identification of a chemoreceptor zinc-binding domain common to cytoplasmic bacterial chemoreceptors. Journal of bacteriology, 193(17), 4338–4345. doi:10.1128/JB.05140-11
Article copy here
Helicobacter pylori perceives the quorum-sensing molecule AI-2 as a chemorepellent via the chemoreceptor TlpB
Rader, B. A., Wreden, C., Hicks, K. G., Sweeney, E. G., Ottemann, K. M., & Guillemin, K. (2011). Helicobacter pylori perceives the quorum-sensing molecule AI-2 as a chemorepellent via the chemoreceptor TlpB. Microbiology (Reading, England), 157(Pt 9), 2445–2455. doi:10.1099/mic.0.049353-0
Article copy here
2010
CheV: CheW-like coupling proteins at the core of the chemotaxis signaling network
Alexander, R. P., Lowenthal, A. C., Harshey, R. M., & Ottemann, K. M. (2010). CheV: CheW-like coupling proteins at the core of the chemotaxis signaling network. Trends in microbiology, 18(11), 494–503. doi:10.1016/j.tim.2010.07.004
Article copy here
A remote CheZ orthologue retains phosphatase function
Lertsethtakarn, P., & Ottemann, K. M. (2010). A remote CheZ orthologue retains phosphatase function. Molecular microbiology, 77(1), 225–235. doi:10.1111/j.1365-2958.2010.07200.x
Article copy here
The chemical-in-plug bacterial chemotaxis assay is prone to false positive responses
Li, J., Go, A. C., Ward, M. J., & Ottemann, K. M. (2010). The chemical-in-plug bacterial chemotaxis assay is prone to false positive responses. BMC research notes, 3(1), 77. doi:10.1186/1756-0500-3-77
Article copy here
2009
Functional analysis of the Helicobacter pylori flagellar switch proteins
Lowenthal, A. C., Hill, M., Sycuro, L. K., Mehmood, K., Salama, N. R., & Ottemann, K. M. (2009). Functional analysis of the Helicobacter pylori flagellar switch proteins. Journal of bacteriology, 191(23), 7147–7156. doi:10.1128/JB.00749-09
Article copy here
A fixed-time diffusion analysis method determines that the three cheV genes of Helicobacter pylori differentially affect motility
Lowenthal, A. C., Simon, C., Fair, A. S., Mehmood, K., Terry, K., Anastasia, S., & Ottemann, K. M. (2009). A fixed-time diffusion analysis method determines that the three cheV genes of Helicobacter pylori differentially affect motility. Microbiology (Reading, England), 155(Pt 4), 1181–1191. doi:10.1099/mic.0.021857-0
Article copy here
The Complete Genome Sequence of Helicobacter pylori Strain G27
Baltrus, D. A., Amieva, M. R., Covacci, A., Lowe, T. M., Merrell, D. S., Ottemann, K. M., … Guillemin, K. (2009). The complete genome sequence of Helicobacter pylori strain G27. Journal of bacteriology, 191(1), 447–448. doi:10.1128/JB.01416-08
Article copy here