Epidemiology, genetics, and ecology of toxigenic Vibrio cholerae

Abstract

Cholera caused by toxigenic Vibrio cholerae is a major public health problem confronting developing countries, where outbreaks occur in a regular seasonal pattern and are particularly associated with poverty and poor sanitation. The disease is characterized by a devastating watery diarrhea which leads to rapid dehydration, and death occurs in 50 to 70% of untreated patients. Cholera is a waterborne disease, and the importance of water ecology is suggested by the close association of V. cholerae with surface water and the population interacting with the water. Cholera toxin (CT), which is responsible for the profuse diarrhea, is encoded by a lysogenic bacteriophage designated CTXPhi. Although the mechanism by which CT causes diarrhea is known, it is not clear why V. cholerae should infect and elaborate the lethal toxin in the host. Molecular epidemiological surveillance has revealed clonal diversity among toxigenic V. cholerae strains and a continual emergence of new epidemic clones. In view of lysogenic conversion by CTXPhi as a possible mechanism of origination of new toxigenic clones of V. cholerae, it appears that the continual emergence of new toxigenic strains and their selective enrichment during cholera outbreaks constitute an essential component of the natural ecosystem for the evolution of epidemic V. cholerae strains and genetic elements that mediate the transfer of virulence genes. The ecosystem comprising V. cholerae, CTXPhi, the aquatic environment, and the mammalian host offers an understanding of the complex relationship between pathogenesis and the natural selection of a pathogen.

FIG. 1

Genetic organization of the TCP pathogenicity island of V. cholerae. Dark boxes show flanking DNA, att sites are shown at both ends, and the putative integrase gene is shown near the right end of the island. The transposase sequence is indicated by a light grey box near the left end of the island. See the text for details.

FIG. 2

Model for the ToxR/ToxT regulatory cascade of V. cholerae. See the text for details.

FIG. 3

Proposed model for the emergence of new strains of toxigenic V. cholerae: possible role of CTXΦ, environmental factors, and the human host in the ecology of toxigenic V. cholerae. See the text for details.