Analysis of Vibrio cholerae Genome Sequences Reveals Unique <i>rtxA</i> Variants in Environmental Strains and an <i>rtxA</i> -Null Mutation in Recent Altered El Tor Isolates

Abstract

Pathogen evolution involves both gain and loss of factors that influence disease. In the environment, bacteria evolve rapidly, with nucleotide diversity arising by genetic modification. Such is occurring with Vibrio cholerae, exemplified by extensive diversity and unique variants of the rtxA-encoded multifunctional autoprocessing RTX (MARTX) toxin among environment-associated strains that cause localized diarrheal outbreaks and food-borne disease. In contrast, seventh pandemic El Tor V. cholerae strains associated with severe diarrhea have changed minimally until the altered El Tor emerged as the most frequent cause of cholera, including in the 2010 Haiti epidemic. These strains have increased virulence attributed to a new variant of the major virulence factor, cholera toxin. It is revealed that these strains also have an inactivated MARTX toxin gene. A similar inactivation occurred during classical cholera pandemics, highlighting that evolution of El Tor cholera is following a similar path of increased dependence on cholera toxin, while eliminating other secreted factors.