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RNA-seq Study of Cholera Pathogen Connects Bacteria-Killing Mechanism to Horizontal Gene Transfer


NEW YORK (GenomeWeb) – Scientists have linked a bacterial weapon system to a regulatory process that drives bacterial evolution in Vibrio cholerae, the pathogen that causes cholera, a new study published today in Science said.

The RNA sequencing study, led by Melanie Blokesch at the Ecole Polytechnique Fédérale in Lausanne, Switzerland, looked into the effects of several regulatory genes on downstream gene expression in the bacterium. One of the genes was TfoX, which was known to regulate a particular mode of horizontal gene transfer. In the paper, the scientists detailed a program of gene expression that leads to natural competence in which V. cholerae, a water-borne pathogen, kills neighboring bacteria and incorporates their genetic material into its own genome.

"There are three modes of horizontal gene transfer: phage transfection, conjugation, and natural competence for transformation," Blokesch told GenomeWeb. "Our study focuses on the latter mechanism. We knew that TfoX expresses many genes that are important to get DNA into the cell, but we didn't know that [the bacteria killing mechanism] was regulated in the same manner by TfoX and two other genes."

This process of natural competence takes place in the V. cholerae's natural aquatic habitat and is induced by chitin, a substance in the outer shells of crustaceous plankton that the bacterium attaches to and feeds on. Colonies on these tiny husks of molted shell can grow as large as several hundred thousand bacteria, or into the millions on the shells of larger crustaceans, like the Dungeness crab used in the study. The bacteria grow into a three-dimensional biofilm, possibly with several different strains present.

"When the bacteria colony grows on the chitin surface, it induces proteins that regulate horizontal gene transfer," Blokesch said. By forcing V. cholerae to express TfoX and other regulatory proteins, the scientists showed that in addition to the machinery to take up the DNA, those genes, kick-started by chitin, also induce the bacteria to produce the type VI secretion system (T6SS), a biological apparatus that is used as a weapon to kill surrounding bacteria. The scientists found that genes producing this protein spike, which the organisms shoot into their microbial neighbors, were also upregulated along with those that facilitate horizontal gene transfer.

With the exception of very closely related organisms, anything is prey for the newly armed bacteria, even other strains of the species. Once lysed, the prey's genes spill out and the predatory bacteria take up the DNA and incorporate it into their own genomes.

"This mechanism allows the transfer of long DNA fragments and we previously showed that this could explain an important emergence of a new variant of V. cholerae," Blokesch said. Natural competence is one way the cholera pathogen actuates horizontal gene transfer, which drives bacterial evolution. Blokesch noted that the bacterium acquired the diarrhea-inducing toxin it produces inside the human intestine from a phage via horizontal gene transfer.

While T6SS mediated-killing followed by the DNA uptake process is primarily linked to the main aquatic habitat of the bacterium, there's a chance it could also happen in the human intestine. Current research suggests that V. cholerae catches a lift into the human intestine while attached to small zooplankton in water. If the pathogen rides in while still in full predator mode, it might still be producing the T6SS weapon, which could kill off the natural gut microbiota and help it colonize the human intestine, Blokesch said. "Obviously, this will be one of the follow-up questions to be investigated."