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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
HP0953 - hypothetical virulence factor overexpresion and localization during Helicobacter pylori infection of gastric epithelium
Nancy K Arteaga-Resendiz, Gerardo E Rodea, Rosa María Ribas-Aparicio, Alma L Olivares-Cervantes, Juan Arturo Castelán-Vega, José de Jesús Olivares-Trejo, Sandra Mendoza-Elizalde, Edgar O López-Villegas, Christian Colín, Pamela Aguilar-Rodea, Alfonso Reyes-López, Marcela Salazar García, Norma Velázquez-Guadarrama
Nancy K Arteaga-Resendiz, Gerardo E Rodea, Alma L Olivares-Cervantes, Sandra Mendoza-Elizalde, Christian Colín, Pamela Aguilar-Rodea, Norma Velázquez-Guadarrama, Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
Nancy K Arteaga-Resendiz, Rosa María Ribas-Aparicio, Juan Arturo Castelán-Vega, 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
José de Jesús Olivares-Trejo, Laboratorio de Adquisición de Hierro, Universidad Autónoma de la Ciudad México, Posgrado Ciencias Genómica, Mexico City 03100, Mexico
Edgar O López-Villegas, Laboratorio Central de Microscopía, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City 11340, Mexico
Alfonso Reyes-López, Centro de estudios económicos y sociales en salud, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
Marcela Salazar García, Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico
Author contributions: Arteaga-Resendiz NK, Rodea GE, Olivares-Cervantes AL, and Colín C performed the experiments, and acquired and analyzed data; Arteaga-Resendiz NK, Rodea GE, Colín C, Olivares-Cervantes AL, Aguilar-Rodea P, Ribas-Aparicio RM, López-Villegas EO, Olivares-Trejo JJ, and Velázquez-Guadarrama N interpreted the data; Reyes-López A and Arteaga-Resendiz NK statistical data analyzed; Rodea GE, Ribas-Aparicio RM, Mendoza-Elizalde S, Salazar García M and Velázquez-Guadarrama N wrote the manuscript; and all authors approved the final version of the article.
Supported by the Federal Funds, HIM/2009/037. SSA851 and HIM / 2014/012. SSA 1098; the grant from Secretaría de Investigación y Posgrado, SIP 20161878; and the Instituto Politécnico Nacional by Consejo Nacional de Ciencia y Tecnología, CB-222180.
Institutional review board statement: The study was reviewed and approved by the Ethics, Biosafety and Scientific committees at the Health Institute approved the experiment (HIM/2009/037. SSA851 and HIM/2014/012. SSA 1098).
Institutional animal care and use committee statement: Animal care was performed under national and institutional policies (NOM-062-ZOO-1999).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to them.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Norma Velázquez-Guadarrama, PhD, Research Scientist, Laboratorio de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Col. Doctores, Alcaldía Cuauhtémoc, Mexico City 06720, Mexico. normave@himfg.edu.mx
Received: January 29, 2022
Peer-review started: January 29, 2022
First decision: April 10, 2022
Revised: April 26, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 7, 2022
ARTICLE HIGHLIGHTS
Research background
Helicobacter pylori (H. pylori) is a bacterium of clinical relevance. Approximately 50% of the worldwide human population is colonized by this bacterium, where up to 3% can develop gastric cancer. Several environmental conditions such as the genetic predisposition of the host, and bacterial virulence factors are directly associated.
Research motivation
H. pylori is a bacterium associated with gastric diseases. This microorganism owns more than 200 hypothetical proteins with functions yet unknown. Some of them could be related to the disease or adaptation to gastric microenvironment. However, in a short-term future, they can be considered as therapeutic targets.
Research objectives
The objective was to characterize the hypothetical protein HP0953, such as structure, location, and expression, to determine if it is a virulence factor employed by H. pylori during infection of against gastric (AGS) cells.
Research methods
Several bioinformatic platforms (SignalP, Expasy, GLYCOPP, I-Tasser) were employed to predict some features of the hypothetical protein HP0953, such as peptide-signaling, three-dimensional structure, and possible post-translational modifications. HP0953 was located during H. pylori infection to AGS cells by transmission electron microscopy, employing a specific antibody for said protein and immunogold technique. The expression of HP0953 during the infection of AGS cell cultures by the bacterium was evaluated by real-time polymerase chain reaction.
Research results
The hypothetical protein HP0953 was observed in the cytoplasm and embedded in the glycocalyx secreted by the bacterium, as well as in the space between the bacterium and the AGS cell. The overexpression of the protein was observed at 12 h of infection. HP0953 was predicted to possess a signal peptide, which can interact with transmembranal regions for its secretion. Additionally, the HP0953 protein acts as like an exotoxin, which can then undergo post-translational modifications, which might then require the eukaryotic cell to be carried out.
Research conclusions
The hypothetical protein HP0953 is a protein located in the periphery of infected cells. It is overexpressed during infection. The in silico analysis revealed prenylation and myristoylation sites. These findings suggest that the protein has a relevant function during the colonization or infection of H. pylori into gastric epithelium.
Research perspectives
Propagate a H. pylori modified strain, which lacks the HP0953 protein. The study will define its functions and establish a new precedent for the study of the pathogenesis of the disease, and its relevance in the adaptation process in the gastric microenvironment.
