Colibactin produced by a honeybee symbiont defends against pathogens and shapes the gut community

Colibactin is a bacterial genotoxin that is linked to colorectal cancer and implicated in interbacterial competition; however, its role in natural communities remains unknown. Frischella perrara, a symbiont living only in honeybee guts, produces colibactin and causes DNA damage. Here, we found that F. perrara mono-colonization reduces bee lifespan but increases survivorship following challenge with an opportunistic pathogen. F. perrara reduces pathogen loads by causing colibactin-dependent DNA damage and prophage induction. clbS, a gene conferring protection from colibactin, is ubiquitous among bacteria restricted to bee guts but is absent from opportunistic colonizers including bee pathogens. Our findings provide evidence that colibactin functions in interbacterial competition, exerts selective pressure on community members, and confers protection against pathogens, while permitting co-evolved gut symbionts to persist.