The role of outer membrane proteins HopI and HopQ of Helicobacter pylori in blocking CagA toxin translocation into gastric cells upon multiple strain infections.
Final Report Abstract
Helicobacter pylori is considered a pathogenic agent, mostly because of the oncogenic properties of one of its toxins, the CagA. At the beginning of this project it was already well stablished that CagA is injected into host cells causing damages in several cellular processes, and it was based on a previously discovered auto-regulation system between the highly pathogenic strains of H. pylori (Type I) and the low pathogenic strains (Type II) that limits the quantities of CagA injected in the host cells and its damage. The objective was to get a better idea of how this process takes place, how the bacteria OMPs are involved and what implications does it bring. We were not able to get to perfect details of the mechanism, but in the process, we learned a great deal on the relation between host cells and H. pylori infection. First, we open the possibility of CagA to have another function, since only a very small amount is injected in the host cells. Nonetheless, the resistance triggered by hopQ to injection of this small quantities does not imply its interaction with CEACAMs on the host cells, and all obtained data hints to a role on the bacteria side rather than the cell directly, possibly with its interactions with other OMPs. We learned that the resistance mechanism is not a “black-and-white” story. We have shown that different combinations of bacteria cause a different response on the translocation resistance. These observations were confirmed while testing strains found in the same host. Previous to these results we envisioned a system in which eradication with antibiotic therapy would be only required as a last resort, and instead considering the possibility of a controlled infection with a type II strain to contain the damages cause by pathogenic strains. This vision has not been erased, but rather it must be modified to a personalized treatment to the microbiota composition with low pathogenic H. pylori strains. We discovered a new method to determine the uniqueness of H. pylori strains and it this way discovered probably a novel mechanism used by H. pylori to control protein functionality by changes on the tryptophan residues at the genetic level. This opens the possibilities to other highly variable bacterial species to adapt to different environments by using tryptophan codon changes. Additionally, thanks to the support with the collaboration with Colombia, we were able to observed that in the Colombian population there is a strong decline of H. pylori -related gastric pathologies and that most of the patients positive for H. pylori presented both type of strains. Additionally, by co-habiting one host, the highly pathogenic strains induced less pro-inflammatory chemokines than those in single type I infections, caused possibly selective pressure by the less pathogenic strains. The work with the isolated strains and their genotyping made possible to design an easy but reliable PCR test to determine the kind of infection a patient has using only the genetic material isolated from the biopsy. Although this test has to be confirmed for different populations, it is a beginning in the understanding of the conflicting relationship of H. pylori and its host, the humans, and how often multiple infections could lead to mild gastric pathologies. We know we are far from creating a novel treatment using less pathogenic strains to control the aggressive behavior of the pathogenic ones in case of disease. However, the fast advancement in molecular techniques are not unknow to us (we already use Nanopore technology for transcriptome analysis) and we hope to identify not only the best combinations of strains in the future, but as well identify other components in the microbiota playing a role in a healthy balance of H. pylori and its host.
Publications
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Detection of cytoplasmic proteins from Helicobacter pylori in Colony Lift Immunoassay. J Microbiol Methods 119, 145–146 (2015)
Rojas-Rengifo, Diana F.; Jaramillo, Carlos A.; Haas, Rainer & Jiménez-Soto, Luisa F.
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Optimized semi-quantitative blot analysis in infection assays using the Stain-Free technology. J Microbiol Methods 126, 38–41 (2016)
Zeitler, Anna F.; Gerrer, Katrin H.; Haas, Rainer & Jiménez-Soto, Luisa F.
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The CagA toxin of Helicobacter pylori: abundant production but relatively low amount translocated. Sci. Rep. 6, 23227 (2016)
Jiménez-Soto, Luisa F. & Haas, Rainer
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Host cell resistance to CagA translocation is as variable as Helicobacter pylori. Matters (2017)
Zeitler, Anna; Gerrer, Katrin; Haas, Rainer & Jiménez-Soto, Luisa
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Genotipificación de cagA y de la región intermedia de vacA en cepas de Helicobacter pylori aisladas de pacientes adultos colombianos y asociación con enfermedades gástricas. Rev. Colomb. Gastroenterol. 33, 103 (2018)
Melo-Narváez, María Camila; Rojas-Rengifo, Diana Fabiola; Jimenéz-Soto, Luisa Fernanda; Delgado Perafán, María Del Pilar; Mendoza de Molano, Belén Elvira; Vera-Chamorro, José Fernando & Jaramillo, Carlos Alberto
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Tryptophan usage by Helicobacter pylori differs among strains. Sci.Rep. 9
Rojas-Rengifo, Diana F.; Ulloa-Guerrero, Cindy P.; Joppich, Markus; Haas, Rainer; del Pilar Delgado, Maria; Jaramillo, Carlos & Jiménez-Soto, Luisa F.
