Horizontal Gene Transfer of the Secretome Drives the Evolution of Bacterial Cooperation and Virulence

Abstract

SummaryBackgroundMicrobes engage in a remarkable array of cooperative behaviors, secreting shared proteins that are essential for foraging, shelter, microbial warfare, and virulence. These proteins are costly, rendering populations of cooperators vulnerable to exploitation by nonproducing cheaters arising by gene loss or migration. In such conditions, how can cooperation persist?ResultsOur model predicts that differential gene mobility drives intragenomic variation in investment in cooperative traits. More mobile loci generate stronger among-individual genetic correlations at these loci (higher relatedness) and thereby allow the maintenance of more cooperative traits via kin selection. By analyzing 21 Escherichia genomes, we confirm that genes coding for secreted proteins—the secretome—are very frequently lost and gained and are associated with mobile elements. We show that homologs of the secretome are overrepresented among human gut metagenomics samples, consistent with increased relatedness at secretome loci across multiple species. The biosynthetic cost of secreted proteins is shown to be under intense selective pressure, even more than for highly expressed proteins, consistent with a cost of cooperation driving social dilemmas. Finally, we demonstrate that mobile elements are in conflict with their chromosomal hosts over the chimeric ensemble's social strategy, with mobile elements enforcing cooperation on their otherwise selfish hosts via the cotransfer of secretome genes with “mafia strategy” addictive systems (toxin-antitoxin and restriction-modification).ConclusionOur analysis matches the predictions of our model suggesting that horizontal transfer promotes cooperation, as transmission increases local genetic relatedness at mobile loci and enforces cooperation on the resident genes. As a consequence, horizontal transfer promoted by agents such as plasmids, phages, or integrons drives microbial cooperation.

Bacterial cooperation controlled by mobile elements: kin selection versus infectivity

“…We conclude that Rankin et al (2010) and Nogueira et al (2009) provide no definitive evidence for kin selection acting in addition to MGEs' infectivity as a mechanism maintaining altruism in cooperative bacteria. We do not deny that altruism among pathogens could evolve by kin selection and there are examples (Koskella et al, 2006;Buckling et al, 2007;Lopez-Villavicencio et al, 2007, 2011.…”

“…We do not deny that altruism among pathogens could evolve by kin selection and there are examples (Koskella et al, 2006;Buckling et al, 2007;Lopez-Villavicencio et al, 2007, 2011. It may well even be that infectivity evolves via kin selection in toxin-producing bacteria, but we contend that the lines of evidence brought in the paper of Rankin et al (2010) and Nogueira et al (2009) are far from sufficient to be conclusive. It is critical to precisely define the conditions under which kin selection could indeed help maintain altruism in these cases, and whether these conditions are met in real cases.…”

“…In the original paper, Nogueira et al (2009) used two lines of evidence in addition to their model to support their contention that kin selection maintains costly common goods in bacterial populations: 1) genes coding for secreted proteins, that is, candidates for cooperative traits, are more likely to be mobile than are other classes of genes; 2) secreted proteins are cheaper to produce than other proteins, thereby reducing c and rendering less stringent the conditions for evolution via kin selection whereby Rb4c. These results are highly interesting and certainly deserve explanation.…”

“…Indeed, if kin cooperate, but also compete for resources, the advantages of cooperation are cancelled. Rankin et al (2010) and Nogueira et al (2009) consider a population structured in distinct patches, and show that relatedness increases within patches due to MGE transmission, but they fail to discuss where competition occurs. For their arguments to work, competition for resource acquisition in bacteria must occur between and not within patches.…”

“…Much of the review is dedicated to a recent paper (Nogueira et al, 2009) exploring the mechanisms that can maintain cooperative traits coded by MGEs in pathogenic bacteria, for example, the secretion of toxins into the environment, which are costly to individuals that bear them but benefit the local population at large, because they allow host infection. They argue that horizontal transfer of MGEs in bacteria promotes cooperation by a kin selection mechanism because transmission increases genetic relatedness at MGEs encoding costly toxins.…”