Building pyramids against the evolutionary emergence of pathogens

Abstract

Mutations allowing pathogens to escape host immunity promote the spread of infectious diseases in heterogeneous host populations and can lead to major epidemics. Understanding the conditions favoring these evolutionary emergences is key for the development of durable control strategies against pathogens. Here we compare the durability of three different control strategies: (i) a mixing strategy where the host population results from the mix of two single-resistant genotypes, (ii) a pyramiding strategy where host resistance is due to a single double-resistant genotype, (iii) a combining strategy where host resistance is due to a mix between a single-resistant genotype and a double-resistant genotype. First, we use evolutionary epidemiology theory to clarify the interplay between demographic stochasticity and evolutionary dynamics to show that the pyramiding strategy always yields lower probability of evolutionary emergence. Second, we confirm experimentally these predictions using virulent bacteriophages introduced in bacterial populations where we can manipulate the diversity and the depth of CRISPR immunity. Our work shows that pyramiding multiple defenses into the same individual host and avoiding mixing with single-defense strategies is a robust way to protect individuals and populations against pathogen evolutionary emergence. These results have practical implications for the optimal deployment of host resistance in agriculture and biotechnology but also for the optimal use of vaccination against human pathogens.

My host’s enemy is my enemy: plasmids carrying CRISPR-Cas as a defence against phages

“…Third, CRISPR-Cas may be favoured to be carried by multi-copy plasmids, in case multiple copies of CRISPR-systems would have synergistic effects and therewith increase phage protection efficiency. Higher phage protection efficiency could be achieved through a higher likelihood for a cell to carry several spacers targeting a given phage (within-cell spacer diversity), which is known to be more efficient in blocking phage evolutionary emergence than population-wide spacer diversity [ 46 ]. However, it is generally unclear if carrying multiple copies of CRISPR-Cas increases within-cell spacer diversity or confers other benefits.…”

Assessing the role of bacterial innate and adaptive immunity as barriers to conjugative plasmids

“…First, our model assumes a maximum of one spacer per cell, which can be sufficient to lead phages to extinction [6, 42]. As within-cell spacer-heterogeneity is even more efficient than population wide-spacer heterogeneity [5], considering multiple spacers per cell could potentially lead plasmids to extinction. Second, while plasmids typically have multiple copies within a cell, we assume these copies are identical.…”

“…Within-cell heterogeneity, characterized by the presence of multiple RM systems per cell [1] or by the acquisition of several spacers targeting the same invader for CRISPR-Cas [4], contributes to a robust immune barrier [5]. Population-wide heterogeneity can also strengthen immunity.…”

“…Approximately 80% of bacteria carry at least one RM system and 40% of bacteria carry at least one CRISPR-Cas system [1] and on average a bacterial cell contains 2.3 RM systems and 0.52 CRISPR-Cas systems [1]. Within-cell heterogeneity, characterized by the presence of multiple RM systems per cell [1] or by the acquisition of several spacers targeting the same invader for CRISPR-Cas [4], contributes to a robust immune barrier [5]. Population-wide heterogeneity can also strengthen immunity.…”