Nasal environment potentiates the pathogenicity of Bordetella pertussis

Pertussis remains a major health concern, as acellular vaccines fail to prevent nasal infection and transmission. The nasal cavity is the primary niche for Bordetella pertussis colonization, but how this particular environment shapes bacterial pathogenicity remains poorly understood. Here we developed bacterial culture conditions that replicate the nasal environment, combining nasal-fluid-like transition metals concentrations with nasal cavity temperature. Using complementary transcriptomic and proteomic approaches, Dual RNA-sequencing, and in vitro and in vivo infection models, we assessed their impact on host-pathogen interactions. Nasal-like conditions reprogram B. pertussis into a state of increased virulence, conferring functional advantages for efficient bacterium-cell interactions and inducing physiological remodeling of human nasal epithelial cells. Finally, we showed that nasal preconditioning promotes efficient early B. pertussis colonization in mice. Altogether, these findings identify the nasal cavity as an instructive niche priming B. pertussis for efficient upper respiratory tract colonization following airborne transmission.