title: Transcriptional Profiling of Type II Toxin-Antitoxin Genes ofHelicobacter pyloriunder Different Environmental Conditions: Identification of HP0967-HP0968 System.
abstract: Helicobacter pyloriis a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence ofH. pyloriin the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin-antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome ofH. pylori26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895. Here we characterized a heretofore undescribed type II TA system inH. pylori, HP0967-HP0968, which is encoded by the bicistronic operonhp0968-hp0967and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed inH. pyloriduring early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, thehp0968-hp0967pair was the most affected under these environmental conditions. Transcription ofhp0968-hp0967was strongly induced in a matureH. pyloribiofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. Thehp0968-hp0967TA system was the most frequent among 317H. pyloristrains isolated from all over the world. This study is the first report on the transcription of type II TA genes inH. pyloriunder different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute abona fidetype II TA system inH. pylori, whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatria, Centro Médico Nacional Siglo XXI, IMSS Mexico City, Mexico.
authors.forename: María G
authors.initials: MG
authors.lastname: Cárdenas-Mondragón
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatria, Centro Médico Nacional Siglo XXI, IMSS Mexico City, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ares
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université UM2, Inserm, U1104, CNRS UMR7280 Marseille, France.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Panunzi
authors.affiliation: Departamento de Microbiología Molecular, Instituto de Biotecnología UNAM Cuernavaca, Mexico.
authors.forename: Sabino
authors.initials: S
authors.lastname: Pacheco
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatria, Centro Médico Nacional Siglo XXI, IMSS Mexico City, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Camorlinga-Ponce
authors.affiliation: Centro de Detección Biomolecular, Benemérita Universidad Autónoma de Puebla Puebla, Mexico.
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Girón
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatria, Centro Médico Nacional Siglo XXI, IMSS Mexico City, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatria, Centro Médico Nacional Siglo XXI, IMSS Mexico City, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: De la Cruz
keywords: H. pylori; HP0967; HP0968; environmental cues; toxin–antitoxin system