Parasite Exposure Drives Selective Evolution of Constitutive versus Inducible Defense

Abstract

In the face of infectious disease, organisms evolved a range of defense mechanisms, with a clear distinction between those that are constitutive (always active) and those that are inducible (elicited by parasites). Both defense strategies have evolved from each other, but we lack an understanding of the conditions that favor one strategy over the other. While it is hard to generalize about their degree of protection, it is possible to make generalizations about their associated fitness costs, which are commonly detected. By definition, constitutive defenses are always "on," and are therefore associated with a fixed cost, independent of parasite exposure. Inducible defenses, on the other hand, may lack costs in the absence of parasites but become costly when defense is elicited through processes such as immunopathology. Bacteria can evolve constitutive defense against phage by modification/masking of surface receptors, which is often associated with reduced fitness in the absence of phage. Bacteria can also evolve inducible defense using the CRISPR-Cas (clustered regularly interspaced short palindromic repeat, CRISPR associated) immune system, which is typically elicited upon infection. CRISPR-Cas functions by integrating phage sequences into CRISPR loci on the host genome. Upon re-infection, CRISPR transcripts guide cleavage of phage genomes. In nature, both mechanisms are important. Using a general theoretical model and experimental evolution, we tease apart the mechanism that drives their evolution and show that infection risk determines the relative investment in the two arms of defense.

Immigration of susceptible hosts triggers the evolution of alternative parasite defence strategies

“…In addition, BIM-4sp was used, which is a WT-derived strain that acquired four spacers against phage DMS3vir. Phage DMS3vir is a previously described mutant of phage DMS3 that cannot enter the lysogenic life cycle owing to mutation of the repressor gene [10,25].…”

“…Migration may also affect the type of host defence that is favoured by selection [6,7]. One reason for this is that host migration may affect the temporal variation in exposure to parasites, as well as the mean force of infection (the frequency at which infections take place), both of which are predicted to influence the relative benefits of defences that are associated with fixed versus parasite-dependent (induced) fitness costs [8][9][10]. This is because induced fitness costs increase as infection frequencies go up, while fixed costs per definition remain the same [8][9][10].…”

“…In response to phage infection, the bacterium Pseudomonas aeruginosa strain UCBPP-PA14 can evolve either surface modification (sm)-or CRISPR-Cas (clustered regularly interspaced short palindromic repeats; CRISPR-associated)-mediated defence [10]. We have previously shown that sm through the loss of the phage receptor is associated with a fixed fitness cost [10][11][12], whereas CRISPR-Cas-mediated defence is associated with an induced fitness cost [10,13].…”

“…We have previously shown that sm through the loss of the phage receptor is associated with a fixed fitness cost [10][11][12], whereas CRISPR-Cas-mediated defence is associated with an induced fitness cost [10,13]. The induced fitness cost of P. aeruginosa CRISPR-Cas may either be because the system is induced upon infection, as is the case in other species [14 -16], or because of phage-induced damage to the host before it is eliminated.…”

“…The induced fitness cost of P. aeruginosa CRISPR-Cas may either be because the system is induced upon infection, as is the case in other species [14 -16], or because of phage-induced damage to the host before it is eliminated. Regardless of the underlying mechanism, the way in which the fitness costs and benefits are manifested has profound impact on the evolution of CRISPR-Cas defence, as the level of phage exposure can tip the balance from CRISPR-Cas to sm [10].…”