Coccoid : A key driver of recurrent infections and a target for novel therapies.

is a globally prevalent pathogen linked to gastritis, peptic ulcers, and gastric cancer, with over half the world's population infected as of recent estimates. While its helical form is well characterized for colonization and virulence, the bacterium's ability to transform into a coccoid morphology under stress conditions remains enigmatic. This review explores the role of the coccoid form in the recurrence of infection, emphasizing its potential as a viable but non-culturable (VBNC) state that facilitates persistence, immune evasion, and reinfection. We highlight the novel role of type-I toxin-antitoxin (TA) systems, especially the /IsoA1 pair, in regulating the coccoid transformation. The /IsoA1 system facilitates the morphological shift to the coccoid form, which is resistant to conventional diagnostics and antibiotics. This immune evasion and antibiotic tolerance results in treatment failure and infection recurrence, even after apparent eradication. Targeting TA systems, alongside other factors, such as peptidoglycan remodeling, could enhance the efficacy of current therapies and reduce relapse rates, offering a pathway for more effective long-term management of infections.