The role of toxin–antitoxin systems in Helicobacter pylori adaptability

Abstract

ABSTRACT Toxin–antitoxin (TA) systems are genetic modules widely distributed across bacterial chromosomes and mobile genetic elements. Initially described as plasmid addiction systems that ensure vertical inheritance through post-segregational killing, they are now recognized as versatile regulators of bacterial adaptability. In Helicobacter pylori, a gastric pathogen infecting nearly half of the global population, multiple TA systems have been experimentally validated, including type I RNA–RNA modules and type II protein–protein pairs. These systems contribute to growth arrest, morphological transition from spiral to coccoid forms, biofilm formation, intracellular survival, and responses to environmental stressors, such as oxidative stress, metal availability, and antibiotic exposure. Type I AapA/IsoA modules have been linked to membrane targeting and dormancy induction, whereas certain Vap-like type II toxins act as ribonucleases and likely contribute to colonization and persistence during infection. Although hundreds of putative TA loci have been identified through bioinformatic analyses, only a small fraction has been functionally characterized, highlighting substantial knowledge gaps. This minireview summarizes experimentally validated TA systems in H. pylori, discusses predicted candidates, and examines their potential roles in pathogen adaptability, emphasizing their relevance to H. pylori persistence and pathogenicity.