Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple CRISPR-Cas Systems

Abstract

SummaryBacteria commonly exist in high cell density populations, making them prone to viral predation and horizontal gene transfer (HGT) through transformation and conjugation. To combat these invaders, bacteria possess an arsenal of defenses, such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their behavior as cell density increases, using quorum sensing (QS) signaling. In this study, we demonstrate that QS regulation results in increased expression of the type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density populations. Strains unable to communicate via QS were less effective at defending against invaders targeted by any of the three CRISPR-Cas systems. Additionally, the acquisition of immunity by the type I-E and I-F systems was impaired in the absence of QS signaling. We propose that bacteria can use chemical communication to modulate the balance between community-level defense requirements in high cell density populations and host fitness costs of basal CRISPR-Cas activity.

The size of the immune repertoire of bacteria

“…High sustained expression of the Cas system in particular may lead to autoimmune like phenotypes, where a bacterium's lifespan is reduced because of the acquisition of spacers from its own genome [21]. This may explain why, in some bacteria, the expression of Cas proteins is controlled by a quorum sensing pathway that is triggered when the density of bacteria is high, making them more susceptible to infections [22][23][24].…”

Ecology Shapes Microbial Immune Strategy: Temperature and Oxygen as Determinants of the Incidence of CRISPR Adaptive Immunity

“…Nev- 22 ertheless, no systematic exploration of the ecological conditions that favor the 23 evolution and maintenance of CRISPR immunity has been made. Additionally, 24 though these previous results appear broadly true [14], no explicit accounting 25 has been made for the potentially confounding effects of phylogeny in linking 26 CRISPR incidence to particular traits. 27 What mechanisms might shape the distribution of CRISPR systems across 28 microbes?…”

“…biofilms) to microbes that tend to live as lone, motile cells (Table 1). That 83 CRISPR is possibly favored in group-living microbes is not entirely surprising, 84 considering the increased risk of viral outbreak at high population density, and 85 that some species up-regulate CRISPR during biofilm formation [25]. 86 Second, we visualized the trait data using t-distributed stochastic neighbor 87 embedding (t-SNE), which is a nonlinear method that can often pick up on more 88 subtle relationships in a dataset (Fig 2; [26]).…”

The Discovery, Mechanisms, and Evolutionary Impact of Anti-CRISPRs

“…Similar to S. thermophilus , Serratia sp. ATCC39006 carries active type I-E, I-F, and III-A CRISPR systems, and these diverse systems were recently discovered to be regulated coordinately by quorum sensing (95). Again, it is unknown whether Acr proteins have driven selection for this Serratia species to carry multiple CRISPR-Cas systems; however, at least one acrF gene ( acrF8 ) is found in Serratia marcescens genomes (49).…”

“…This shows that Acr proteins can be overwhelmed by shifting intracellular Cas protein concentrations, and suggests the possibility for bacteria to overcome anti-CRISPRs by overexpressing components of CRISPR-Cas systems. Multiple papers have reported different pathways involved in regulation of CRISPR-Cas systems in diverse bacteria (95–98). In each case, these systems are dynamically regulated, suggesting a cost to constitutive CRISPR expression.…”