Outbreaks of cholera are caused by the highly transmissive pathogenVibrio cholerae. Here, a transposon screen revealed that inactivation of theV. choleraemotility-linked genemotVincreases infant mouse intestinal colonization. Compared to wild-typeV. cholerae, a ΔmotVmutant, which exhibits heightened motility in the form of constitutive straight swimming, localizes to the crypts earlier in infection and over a larger area of the small intestine. Aberrant localization of the mutant was associated with an increased number ofV. choleraeinitiating infection, and elevated pathogen burden, diarrhea, and lethality. Moreover, the deletion ofmotVcausesV. choleraeto transmit from infected suckling mice to naïve littermates more efficiently. Even in the absence of cholera toxin, the ΔmotVmutant continues to transmit between animals, although less than in the presence of toxin, indicating that phenotypes other than cholera toxin-driven diarrhea contribute to transmission. Collectively, this work provides experimental evidence linking intra-animal bottlenecks, colonization, and disease to inter-animal transmission.
