Immune Lag Is a Major Cost of Prokaryotic Adaptive Immunity During Viral Outbreaks

Abstract

CRISPR adaptive immune systems enable bacteria and archaea to efficiently respond to viral pathogens by creating a genomic record of previous encounters. These systems are broadly distributed across prokaryotic taxa, yet are surprisingly absent in a majority of organisms, suggesting that the benefits of adaptive immunity frequently do not outweigh the costs. Here, combining experiments and models, we show that a delayed immune response which allows viruses to transiently redirect cellular resources to reproduction, which we call "immune lag", is extremely costly during viral outbreaks, even to completely immune hosts. Critically, the costs of lag are only revealed by examining the non-equilibrium dynamics of a host-virus system occurring immediately after viral challenge. Lag is a basic parameter of microbial defense, relevant to all intracellular, post-infection antiviral defense systems, that has to-date been largely ignored by theoretical and experimental treatments of host-phage systems.

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

“…It is possible that viral abundance rarely reaches levels in nature that are sufficient to preclude an effective CRISPR-Cas response, even if such densities are readily achievable in laboratory experiments. 9,10,24 Future work may reveal the ecological differences between CRISPR-Cas types, as different types are likely to coevolve with viruses in fundamentally different ways. 25 Genomic evidence demonstrates that CRISPR-Cas systems are frequently acquired and lost, 26,27 and empirical studies show that they can be mobilized through HGT.…”

Ecological drivers of CRISPR immune systems

“…However, the CRISPR systems distribute unevenly across the prokaryotic phylogeny and environments [41] despite these high rates of HGT. This apparent paradox has been explained by direct fitness costs of the CRISPR system or reduced benefit due to competition from other immune systems [14,18,[42][43][44]. For instance, acquiring self-targeting spacers is deleterious to the host [45][46][47]; CRISPR may prevent HGT so that the acquisition of advantageous mobile genetic elements (MGEs) is limited [48][49][50][51]; CRISPR shows negative epistasis with host genes in some cases [41,52].…”

“…Studies have shown that CRISPR-Cas-mediated immunity in bacteria comes with inducible costs upon phage infection [9, 10]. These costs arise directly from the expression of the CRISPR array and cas genes upon infection [11, 12] as well as indirectly from the time lag between the start of phage gene expression and the clearance by the CRISPR system [13, 14]. Even short-term expression of phage genes can be toxic and leads to reduced fitness of the host [13].…”