OmpR-mediated activation of the type Vl secretion system drives enhanced acid tolerance in Cronobacter

Cronobacter (7 species) are prevalent foodborne pathogens with a remarkable capacity to adapt to acidic environments. This resilience enables them to persist in both food matrices and host organisms. Here we investigated the role of the 2-component system response regulator OmpR in the acid tolerance of Cronobacter. Under acid stress, Cronobacter malonaticus demonstrated significantly elevated expression of ompR and type VI secretion system (T6SS) genes, as well as a marked decrease in the survival of OmpR or T6SS structure gene mutants, indicating the pivotal role of OmpR and T6SS in acid tolerance. Notably, OmpR markedly enhanced the T6SS expression by binding specifically to its promoter, and the activated T6SS expedited adaptation to acidic environments and facilitated biofilm formation, thereby aiding Cronobacter's survival under acidic conditions. Moreover, knocking out ompR in 6 additional Cronobacter species resulted in decreased T6SS expression and tolerance to acid stress than their wild-type strains, which further solidifies the widespread nature of the acid tolerance mechanism predicated on the activation of T6SS by OmpR in Cronobacter spp. A comprehensive understanding of the adaptation mechanisms employed by Cronobacter spp. in acidic conditions will provide a theoretical foundation for managing their contamination in acidic food matrices and preventing infection outbreaks in the infant gastrointestinal tract.