Attack of the Clones: What Causes Population Structure in Bacteria and How Can We Use It?*

In most pathogenic bacteria, the population is made up of multiple distinct lineages or ‘clones’ which are associated with properties like virulence or drug resistance. For the most part, this structure has been taken for granted and its root causes not been examined. We have recently shown, using the pneumococcus as a model organism, that we can explain which clones are present in a community with a simple model of negative frequency dependent selection operating on a subset of the genome: namely the accessory genome of loci not present in all isolates of the species. Moreover, we can use this to predict the consequences of removing some clones, for instance through vaccination. This can be achieved either through a game theory approach using the replicator equation, or through quadratic programming to determine how the equilibrium properties of the population as a whole can be restored by altering the proportions of each clone. Finally the existence of clones offers an opportunity to use emerging DNA sequencing technologies to rapidly detect them in clinical samples, which could be useful for detecting and responding to drug resistant threats.