Dynamics of immune memory and learning in bacterial communities

Abstract

From bacteria to humans, adaptive immune systems provide learned memories of past infections. Despite their vast biological differences, adaptive immunity shares features from microbes to vertebrates such as emergent immune diversity, long-term coexistence of hosts and pathogens, and fitness pressures from evolving pathogens and adapting hosts, yet there is no conceptual model that addresses all of these together. To this end, we propose and solve a simple phenomenological model of CRISPR-based adaptive immunity in microbes. We show that in coexisting phage and bacteria populations, immune diversity in both populations is coupled and emerges spontaneously, that bacteria track phage evolution with a context-dependent lag, and that high levels of diversity are paradoxically linked to low overall CRISPR immunity. We define average immunity, an important summary parameter predicted by our model, and use it to perform synthetic time-shift analyses on available experimental data to reveal different modalities of coevolution. Finally, immune cross-reactivity in our model leads to qualitatively different states of evolutionary dynamics, including an influenza-like traveling wave regime that resembles a similar state in models of vertebrate adaptive immunity. Our results show that CRISPR immunity provides a tractable model, both theoretically and experimentally, to understand general features of adaptive immunity.

Transient eco-evolutionary dynamics early in a phage epidemic have strong and lasting impact on the long-term evolution of bacterial defences

“…Long-term ongoing CRISPR-phage coevolution has so far only been observed for Streptococcus thermophilus and its virulent phage 2972, resulting in an arms race dynamics that may ultimately lead to phage extinction as phage accumulate costly mutations and face an increasingly diverse spacer repertoire in the bacterial population [30][31][32]. A number of models have been developed to explore conditions where bacteria with CRISPR immunity and their phage can coexist, with or without coevolution [33][34][35][36], which may be mediated through CRISPR loss [16,37], exposure to a greater number of diverse phage species [38], or a spatial organisation of the bacteria and phage [28,39,40]. Future empirical studies are needed to explore patterns of CRISPR-phage coexistence and coevolution in environments with greater ecological complexity.…”