Cracking the cholera code

Many bacteria use chemical signals to coordinate group behaviour. This process is called quorum sensing. Vibrio cholerae, the bacterium which causes cholera, is ‘bilingual’ – it uses two distinct signalling molecules to suppress its virulence. One of these signals is a molecule that many species of bacteria use for quorum sensing, but the identity of the second signal has remained a mystery. In the latest issue of Nature, Higgins et al. report the structure of this second signal. Their discovery represents a new structural class of quorum-sensing signal that may be exclusive to Vibrio bacteria, making it a possible lead for drug discovery.

The major Vibrio cholerae autoinducer and its role in virulence factor production. 2007 Nature 450: 883

Abstract: Vibrio cholerae, the causative agent of the human disease cholera, uses cell-to-cell communication to control pathogenicity and biofilm formation. This process, known as quorum sensing, relies on the secretion and detection of signalling molecules called autoinducers. At low cell density V. cholerae activates the expression of virulence factors and forms biofilms. At high cell density the accumulation of two quorum-sensing autoinducers represses these traits. These two autoinducers, cholerae autoinducer-1 (CAI-1) and autoinducer-2 (AI-2), function synergistically to control gene regulation, although CAI-1 is the stronger of the two signals. V. cholerae AI-2 is the furanosyl borate diester (2S,4S)-2-methyl-2,3,3,4-tetrahydroxytetrahydrofuran borate. Here we describe the purification of CAI-1 and identify the molecule as (S)-3-hydroxytridecan-4-one, a new type of bacterial autoinducer. We provide a synthetic route to both the R and S isomers of CAI-1 as well as simple homologues, and we evaluate their relative activities. Synthetic (S)-3-hydroxytridecan-4-one functions as effectively as natural CAI-1 in repressing production of the canonical virulence factor TCP (toxin co-regulated pilus). These findings suggest that CAI-1 could be used as a therapy to prevent cholera infection and, furthermore, that strategies to manipulate bacterial quorum sensing hold promise in the clinical arena.

Also: Cooperation and conflict in quorum-sensing bacterial populations. 2007 Nature 450: 411
Abstract: It has been suggested that bacterial cells communicate by releasing and sensing small diffusible signal molecules in a process commonly known as quorum sensing (QS). It is generally assumed that QS is used to coordinate cooperative behaviours at the population level. However, evolutionary theory predicts that individuals who communicate and cooperate can be exploited. Here we examine the social evolution of QS experimentally in the opportunistic pathogen Pseudomonas aeruginosa, and show that although QS can provide a benefit at the group level, exploitative individuals can avoid the cost of producing the QS signal or of performing the cooperative behaviour that is coordinated by QS, and can therefore spread. We also show that a solution to the problem of exploitation is kin selection, if interacting bacterial cells tend to be close relatives. These results show that the problem of exploitation, which has been the focus of considerable attention in animal communication, also arises in bacteria.

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One Comment

  • Amiya Sarkar says:

    The QS phenomenon is interesting. On the one hand it reflects the ‘colony behavior’ of ants and bees; on the other hand the complex molecular computational mathematics it employs is equally interesting.