Ingestion of Bacillus cereus spores dampens the immune response to favor bacterial persistence

Strains of the Bacillus cereus (Bc) group are sporulating bacteria commonly associated with foodborne outbreaks. Spores are dormant cells highly resistant to extreme conditions. Nevertheless, the pathological processes associated with the ingestion of either vegetative cells or spores remain poorly understood. Here, we demonstrate that while ingestion of vegetative bacteria leads to their rapid elimination from the intestine of Drosophila melanogaster, a single ingestion of spores leads to the persistence of bacteria for at least 10 days. We show that spores do not germinate in the anterior part of the intestine which bears the innate immune defenses. Consequently, spores reach the posterior intestine where they germinate and activate both the Imd and Toll immune pathways. Unexpectedly, this leads to the induction of amidases, which are negative regulators of the immune response, but not to antimicrobial peptides. Thereby, the local germination of spores in the posterior intestine dampens the immune signaling that in turn fosters the persistence of Bc bacteria. This study provides evidence for how Bc spores hijack the intestinal immune defenses allowing the localized birth of vegetative bacteria responsible for the digestive symptoms associated with foodborne illness outbreaks.