Antibiotics Impact the Cytotoxicity and Cytopathic Effect of Helicobacter pylori Extracellular Vesicles Against Gastric Cells

Helicobacter pylori is a spiral microorganism capable of inducing a range of gastric diseases. Among different virulence determinants produced by this bacterium, VacA and CagA are of critical importance for the development of these conditions. Taking into account the ability to chronically colonize the stomach, drug-resistant strains of this pathogen can be repeatedly exposed to subinhibitory antibiotic concentrations, which in turn may reduce or enhance their extracellular vesicles (EVs)-derived virulence towards gastric cells. With the use of different experimental techniques, we were the first to demonstrate that subinhibitory antibiotic concentrations modify both the cytotoxicity and cytopathic effect induced by EVs of H. pylori in gastric cells. The ability to induce vacuolization and the hummingbird phenotype in gastric cells presented an antibiotic-specific pattern. At the highest doses tested, all EV types induced phenotypic changes and cytotoxicity in gastric cells; however, the highest lethal effect was observed for EVs isolated from native (antibiotic-unexposed) cells. This suggests that short-term exposure of H. pylori to subinhibitory antibiotic concentrations does not translate into exacerbation of its EVs-dependent virulence. Nevertheless, extensive research in this area is undoubtedly needed to confirm these observations.