Transcriptional Profiling of Type II Toxin-Antitoxin Genes of under Different Environmental Conditions: Identification of HP0967-HP0968 System.

is 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 of in 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 of 26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895. Here we characterized a heretofore undescribed type II TA system in , HP0967-HP0968, which is encoded by the bicistronic operon and 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 in during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the pair was the most affected under these environmental conditions. Transcription of was strongly induced in a mature biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The TA system was the most frequent among 317 strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a type II TA system in , whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.