Estion of why parasites harm the very source of their livelihoods. The development of evolutionary Anisomycin site theory to explain virulence ( parasite-induced harm to the host) hasa long history. Theories for the evolution of virulence can be categorized into four broad hypotheses [77,78] under which high virulence is attributed variously to: (i) novel host arasite associations [79,80]; (ii) transmission irulence trade-offs [81]; (iii) coincidental evolution of virulence factors [82,83]; and (iv) short-term within-host evolution [84]. For many infectious diseases, social interactions among parasites and virulence are coupled, but the nature of this relationship varies according to the type of interactions involved and who the interaction partners are. The most influential theoretical framework for virulence evolution centres on virulence being maintained as a result of an unavoidable constraint linking the benefits of transmission with the costs of virulence. In this view, virulence (measured as host death) is an unavoidable cost of the host exploitation required for transmission to new hosts [85?8]. If the costs of increasing exploitation accelerate more rapidly than the transmission benefits of increasing exploitation, then natural selection favours an intermediate level of host exploitation (optimal virulence) [81,89]. Following from this premise, the LM22A-4 custom synthesis relatedness of co-infecting parasite genotypes can modulate the best or evolutionary stable strategy of virulence, depending on the nature of social interactions among co-infecting parasites (figure 2). When co-infecting genotypes have direct control over their mechanisms of host exploitation, the benefits of increased exploitation are felt by the individuals responsible whereas the costs of virulence are shared by all, favouring greater virulence than that of parasites in single genotype infections [86 ?9]. By contrast, if co-infecting parasites work collectively to exploit the host (for example, via the secretion of shared extracellular digestive enzymes), then the benefits of exploitation become collectivized and mixed infections can select for `non-producer’ cheats that attenuate virulence [90]. In both scenarios, the spread of cheats (either over- or under-exploiters) undermines the productivity of the infection as a whole [56,88] but has opposite consequences for virulence.(a) virulence(b)(c)rstb.royalsocietypublishing.orgrelatednessrelatednessrelatednessFigure 2. Theoretical relationships between virulence and relatedness under conditions of: (a) individual exploitation (virulence maximized at low relatedness) (b) collective exploitation (virulence maximized at high relatedness) (c) spiteful interactions, e.g. when harming competitors trades off against replication that causes virulence. (summarized by [16]).secretion of costly `public goods’ molecules. These molecules generate a range of benefits to any neighbouring cell that are suitably equipped to profit. For example, public goods molecules may scavenge for limiting resources (e.g. siderophores), aid in the construction of biofilms (e.g. adhesive polymers), kill competing lineages (e.g. bacteriocins) or enhance host exploitation (e.g. digestive enzymes, toxins). Because these molecules are individually costly to produce and yet return a collective benefit, they have become a focus in the study of bacterial cooperation. Among the best-studied model system for public goods cooperation is iron scavenging by secreted siderophores in the oppo.Estion of why parasites harm the very source of their livelihoods. The development of evolutionary theory to explain virulence ( parasite-induced harm to the host) hasa long history. Theories for the evolution of virulence can be categorized into four broad hypotheses [77,78] under which high virulence is attributed variously to: (i) novel host arasite associations [79,80]; (ii) transmission irulence trade-offs [81]; (iii) coincidental evolution of virulence factors [82,83]; and (iv) short-term within-host evolution [84]. For many infectious diseases, social interactions among parasites and virulence are coupled, but the nature of this relationship varies according to the type of interactions involved and who the interaction partners are. The most influential theoretical framework for virulence evolution centres on virulence being maintained as a result of an unavoidable constraint linking the benefits of transmission with the costs of virulence. In this view, virulence (measured as host death) is an unavoidable cost of the host exploitation required for transmission to new hosts [85?8]. If the costs of increasing exploitation accelerate more rapidly than the transmission benefits of increasing exploitation, then natural selection favours an intermediate level of host exploitation (optimal virulence) [81,89]. Following from this premise, the relatedness of co-infecting parasite genotypes can modulate the best or evolutionary stable strategy of virulence, depending on the nature of social interactions among co-infecting parasites (figure 2). When co-infecting genotypes have direct control over their mechanisms of host exploitation, the benefits of increased exploitation are felt by the individuals responsible whereas the costs of virulence are shared by all, favouring greater virulence than that of parasites in single genotype infections [86 ?9]. By contrast, if co-infecting parasites work collectively to exploit the host (for example, via the secretion of shared extracellular digestive enzymes), then the benefits of exploitation become collectivized and mixed infections can select for `non-producer’ cheats that attenuate virulence [90]. In both scenarios, the spread of cheats (either over- or under-exploiters) undermines the productivity of the infection as a whole [56,88] but has opposite consequences for virulence.(a) virulence(b)(c)rstb.royalsocietypublishing.orgrelatednessrelatednessrelatednessFigure 2. Theoretical relationships between virulence and relatedness under conditions of: (a) individual exploitation (virulence maximized at low relatedness) (b) collective exploitation (virulence maximized at high relatedness) (c) spiteful interactions, e.g. when harming competitors trades off against replication that causes virulence. (summarized by [16]).secretion of costly `public goods’ molecules. These molecules generate a range of benefits to any neighbouring cell that are suitably equipped to profit. For example, public goods molecules may scavenge for limiting resources (e.g. siderophores), aid in the construction of biofilms (e.g. adhesive polymers), kill competing lineages (e.g. bacteriocins) or enhance host exploitation (e.g. digestive enzymes, toxins). Because these molecules are individually costly to produce and yet return a collective benefit, they have become a focus in the study of bacterial cooperation. Among the best-studied model system for public goods cooperation is iron scavenging by secreted siderophores in the oppo.