Interrupting Cholera’s Conversation

CAI-1 a new quorum sensing molecule in Vibrio cholerae

Researchers have deciphered the molecular language that cholera bacteria use to coordinate their infectivity. The bacteria use this chemical communication to signal their presence to one another, so that they can plan as a group when to be most virulent and when to escape their host to find new victims.

Howard Hughes Medical Institute investigator Bonnie Bassler and her colleagues at Princeton University reported their findings in the November 15, 2007, issue of the journal Nature.

Bassler and her colleagues have long studied a type of bacterial chemical conversation known as quorum sensing. This process depends on the bacteria releasing signaling chemicals called autoinducers into their environment, and subsequently detecting and responding to the build up of these molecules to coordinate with one another to ensure maximum infectivity and other group behaviors.

“We had shown that cholera had quorum sensing, and we had produced a mutant form of cholera that couldn't perform quorum sensing properly, which affected virulence,” said Bassler. “This finding told us that there must be an autoinducer molecule that this mutant couldn't make that had a role in virulence, but we had no idea what that molecule was.”

Bassler explained that the way the cholera bacteria use that molecule suggested it could make a useful treatment. “When people first get cholera, the bacteria immediately stick to the intestine in a structure called a biofilm and they release toxins,” she said. “During this time, they are multiplying rapidly and also releasing the autoinducer molecule. When the bacteria reach high cell numbers, the high concentration of the autoinducer molecule represses virulence and stops biofilm formation, enabling the bacteria to escape into the environment to spread to other people. So, if we could isolate and purify this molecule, and supply it to the bacteria to get them to prematurely terminate virulence, we thought it could be used as a treatment approach.”

Through their mutational studies, the researchers had identified the gene that codes for the enzyme that makes the unknown molecule. They inserted that gene into the gut bacterium E. coli, transforming the bacterium into a biological factory for large amounts of the chemical. That strategy allowed them to purify the chemical, which they called CAI-1, and analyze its molecular structure.

“We know that there are molecules analogous to CAI-1 that are very species-specific, and we also understand that there are molecules that are generic and enable inter-species communication. Together, they give bacteria a multicellular character. And the fact that we are coming to understand this communication and even learn how to manipulate it both for medical and industrial purposes makes this a very exciting time for this research field.

Source: Howard Huges Medical Institute

Aporte: Guillermo Figueroa