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Your Cheatin’ Chromosome

10/11/2012
Jim Kling

To work with other members of their community, some bacteria rely on quorum sensing to regulate the group’s gene expression. So, what happens when some decide to be less than cooperative?


Using a system of cellular communication called quorum sensing, bacteria cooperate with each other by secreting signaling molecules that regulate the gene expression of other members of their community. But not every bacterium within these communities is cooperative. Mutant cheaters receive these signals but disregard them, giving them a potential metabolic advantage over their neighbors.

A skim milk plate showing at least two protease-negative colonies (cheaters) adjacent to protease producers (cooperators). In the experiments, cheaters benefit from the secreted proteases produced by cooperators. Source: Ajai Dandekar, University of Washington





Such a system could be overwhelmed by slackers, but it evidently doesn’t happen often. The reason may be that the underlying genetic mutation also short circuits some normal metabolic genes, according to a study published online today in Science (1).

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“The trick to stabilizing cooperation, at least in these laboratory experiments, is to co-regulate the public and private goods. There’s an inherent ability within these cells to restrict cheating,” said study author E. Peter Greenberg, professor of microbiology at the University of Washington School of Medicine.

The team studied Pseudomonas aeruginosa, a virulent microbe that plagues cystic fibrosis patients, burn victims, and the immunosuppressed. When a community of P. aeruginosa reaches a threshold density, they signal to one another to begin the production of extracellular enzymes that benefit the entire population.

In this case, quorum sensing controls the expression of 325 different genes, or about 5% of the bacterial genome. Most of those genes code for proteins that are secreted into the environment, where they can serve a public good that is beneficial to all cells in the community. For example, the cells can’t absorb large proteins, so some secreted enzymes digest those proteins into easier-to-absorb amino acids.

In contrast, mutant cheaters disassemble part of the quorum-sensing pathway, avoiding the associated metabolic cost of producing these secreted proteins. Under the right conditions in a media of the milk protein casein, cheaters can become prolific enough to collapse the bacteria community.

So, why this doesn’t happen more frequently in nature? Greenburg and colleagues said that it’s because mutants didn’t just stop producing a single enzyme, they stopped expressing dozens of genes that are regulated by the quorum-sensing pathway. And the products of some of those genes are necessary for the metabolic break-down of nutrients such as the nucleotide adenosine.

Sure enough, when they repeated the experiment in a growth media with adenosine present, the mutants didn’t fare as well. When adenosine made up more than 50% of the nutrients, mutants topped out at only 0.2% of the population, presumably because their inability to utilize adenosine blunted the mutation’s survival advantage.

It remains to be seen if a similar process occurs in more natural settings, but if so, the results have implications for the understanding of bacterial behavior, and potentially for therapeutics. “It raises the possibility that maybe in the future we’ll know enough about the sociality and economics of bacteria to be able to control and manipulate infections. Maybe we’ll be able to manipulate the conditions to encourage cheaters to overtake cooperators and destroy their own infection,” said Greenberg.

Reference

1. Dandekar, A.A., S. Chugani, and E.P. Greenberg. 2012. “Bacterial quorum sensing and metabolic incentives to cooperate.” Science 338:264-266. Published online October 11, 2012.

Keywords:  bacteria