Coccoid forms of Helicobacter pylori are the morphologic manifestation of cell death

Helicobacter pylori can transform from its normal helical bacillary morphology to a coccoid morphology. Since this coccoid form cannot be cultured in vitro, it has been speculated that it is a dormant form potentially involved in the transmission of H. pylori and in a patient's relapse after antibiotic therapy. In this study we determined the effects of aging, temperature, aerobiosis, starvation, and antibiotics on the morphologic conversion rate and culturability of H. pylori. Aerobiosis and the addition of a bactericidal antibiotic to the culture medium resulted in the highest conversion rate. During the conversion to coccoid forms, the cultures always lost culturability at the stage where 50% of the organisms were still in bacillary form; this result indicated that culturability and coccoid morphology are two separate but related entities. Independent of the conditions used to induce the conversion into coccoids, the morphological conversion was accompanied by several marked antigenic and ultrastructural changes. Also, both the total amounts and the integrity of RNA and DNA were significantly reduced in coccoid forms. With the potential-sensitive probe diOC(5)-3, a clear loss of membrane potential in coccoid forms was observed. Inhibition of protein or RNA synthesis by the addition of bacteriostatic antibiotics did not prevent the conversion to coccoid forms but resulted in an increased conversion rate. Hence, we conclude that conversion of H. pylori from the bacillary to the coccoid form is a passive process that does not require protein synthesis. Our data suggest that the coccoid form of H. pylori is the morphologic manifestation of bacterial cell death.