HP0953 - hypothetical virulence factor overexpresion and localization during Helicobacter pylori infection of gastric epithelium.

Autor:	Arteaga-Resendiz NK; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico.; Posgrado en Biomedicina y Biotecnología Molecular, Laboratorio de Producción y Control de Biológicos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Rodea GE; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Ribas-Aparicio RM; Posgrado en Biomedicina y Biotecnología Molecular, Laboratorio de Producción y Control de Biológicos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Olivares-Cervantes AL; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Castelán-Vega JA; Posgrado en Biomedicina y Biotecnología Molecular, Laboratorio de Producción y Control de Biológicos, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Olivares-Trejo JJ; Laboratorio de Adquisición de Hierro, Universidad Autónoma de la Ciudad México, Posgrado Ciencias Genómica, Mexico City 03100, Mexico., Mendoza-Elizalde S; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., López-Villegas EO; Laboratorio Central de Microscopía, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico., Colín C; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Aguilar-Rodea P; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Reyes-López A; Centro de estudios económicos y sociales en salud, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Salazar García M; Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico., Velázquez-Guadarrama N; Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico. normave@himfg.edu.mx.
Jazyk:	angličtina
Zdroj:	World journal of gastroenterology [World J Gastroenterol] 2022 Aug 07; Vol. 28 (29), pp. 3886-3902.
DOI:	10.3748/wjg.v28.i29.3886
Abstrakt:	Background: The high prevalence and persistence of Helicobacter pylori ( H. pylori ) infection, as well as the diversity of pathologies related to it, suggest that the virulence factors used by this microorganism are varied. Moreover, as its proteome contains 340 hypothetical proteins, it is important to investigate them to completely understand the mechanisms of its virulence and survival. We have previously reported that the hypothetical protein HP0953 is overexpressed during the first hours of adhesion to inert surfaces, under stress conditions, suggesting its role in the environmental survival of this bacterium and perhaps as a virulence factor. Aim: To investigate the expression and localization of HP0953 during adhesion to an inert surface and against gastric (AGS) cells. Methods: Expression analysis was performed for HP0953 during H. pylori adhesion. HP0953 expression at 0, 3, 12, 24, and 48 h was evaluated and compared using the Kruskal-Wallis equality-of-populations rank test. Recombinant protein was produced and used to obtain polyclonal antibodies for immunolocalization. Immunogold technique was performed on bacterial sections during adherence to inert surfaces and AGS cells, which was analyzed by transmission electron microscopy. HP0953 protein sequence was analyzed to predict the presence of a signal peptide and transmembrane helices, both provided by the ExPASy platform, and using the GLYCOPP platform for glycosylation sites. Different programs, via , I-TASSER, RaptorX, and HHalign-Kbest, were used to perform three-dimensional modeling. Results: HP0953 exhibited its maximum expression at 12 h of infection in gastric epithelium cells. Immunogold technique revealed HP0953 localization in the cytoplasm and accumulation in some peripheral areas of the bacterial body, with greater expression when it is close to AGS cells. Bioinformatics analysis revealed the presence of a signal peptide that interacts with the transmembrane region and then allows the release of the protein to the external environment. The programs also showed a similarity with the Tip-alpha protein of H. pylori . Tip-alpha is an exotoxin that penetrates cells and induces tumor necrosis factor alpha production, and HP0953 could have a similar function as posttranslational modification sites were found; modifications in turn require enzymes located in eukaryotic cells. Thus, to be functional, HP0953 may necessarily need to be translocated inside the cell where it can trigger different mechanisms producing cellular damage. Conclusion: The location of HP0953 around infected cells, the probable posttranslational modifications, and its similarity to an exotoxin suggest that this protein is a virulence factor. Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article. (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
Databáze:	MEDLINE
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