Hypermutability impedes cooperation in pathogenic bacteria

When the supply of beneficial mutations limits adaptation, bacterial mutator alleles can reach high frequencies by hitchhiking with advantageous mutations [1-9]. However, when populations are well adapted to their environments, the increased rate of deleterious mutations makes hypermutability selectively disadvantageous [6, 7, 10, 11]. Here, we consider a further cost of hypermutability: its potential to break down cooperation (group-beneficial behavior that is costly to the individual [12-14]). This probably occurs for three reasons. First, an increased rate at which 'cheating' genotypes are generated; second, an increased probability of producing efficient cheats; and third, a decrease in relatedness [15-18] (not addressed in the present study). We used Pseudomonas aeruginosa's production of extracellular iron-scavenging molecules, siderophores, to determine if cheating evolved more readily in mutator populations. Siderophore production is costly to individual bacteria but benefits all nearby cells. Siderophore-deficient cheats therefore have a selective advantage within populations [18]. We observed the de novo evolution and subsequent increase in frequency of siderophore cheats within both wild-type and mutator populations for 200 generations. Cheats appeared and increased in frequency more rapidly in mutator populations. The presence of cheats was costly to the group, as shown by a negative correlation between cheat frequency and population density.