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Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions.

ABSTRACT: Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence^1-8, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes^9-14, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation^15-20. In this study, we used synthetic oscillatory gene regulatory networks (GRNs) based on CRISPR interference together with live cell microscopy and cell tracking within microfluidics devices to mimic and test the biological function of bacterial phenotypic variation. We provide a universally applicable approach for engineering intricate GRNs using only two components: dCas9 and extended sgRNAs (ext-sgRNAs). Our findings demonstrate that variation in capsule production is beneficial for pneumococcal fitness in traits associated with pathogenesis providing conclusive evidence for this longstanding question.

SUBMITTER: Rueff AS

PROVIDER: S-EPMC10312626 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions.

Rueff Anne-Stéphanie AS van Raaphorst Renske R Aggarwal Surya S Santos-Moreno Javier J Laloux Géraldine G Schaerli Yolanda Y Weiser Jeffrey N JN Veening Jan-Willem JW

bioRxiv : the preprint server for biology 20230603

Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence1-8, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes9-14, but the exact relationship between variation a ...[more]

PMID: 37398107

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Project description:Robustness and plasticity are essential features that allow biological systems to cope with complex and variable environments. In a constant environment, robustness, i.e., insensitivity of phenotypes, is expected to increase, whereas plasticity, i.e., the changeability of phenotypes, tends to diminish. Under a variable environment, existence of plasticity will be relevant. The robustness and plasticity, on the other hand, are related to phenotypic variances. As phenotypic variances decrease with the increase in robustness to perturbations, they are expected to decrease through the evolution. However, in nature, phenotypic fluctuation is preserved to a certain degree. One possible cause for this is environmental variation, where one of the most important "environmental" factors will be inter-species interactions. As a first step toward investigating phenotypic fluctuation in response to an inter-species interaction, we present the study of a simple two-species system that comprises hosts and parasites. Hosts are expected to evolve to achieve a phenotype that optimizes fitness. Then, the robustness of the corresponding phenotype will be increased by reducing phenotypic fluctuations. Conversely, plasticity tends to evolve to avoid certain phenotypes that are attacked by parasites. By using a dynamic model of gene expression for the host, we investigate the evolution of the genotype-phenotype map and of phenotypic variances. If the host-parasite interaction is weak, the fittest phenotype of the host evolves to reduce phenotypic variances. In contrast, if there exists a sufficient degree of interaction, the phenotypic variances of hosts increase to escape parasite attacks. For the latter case, we found two strategies: if the noise in the stochastic gene expression is below a certain threshold, the phenotypic variance increases via genetic diversification, whereas above this threshold, it is increased mediated by noise-induced phenotypic fluctuation. We examine how the increase in the phenotypic variances caused by parasite interactions influences the growth rate of a single host, and observed a trade-off between the two. Our results help elucidate the roles played by noise and genetic mutations in the evolution of phenotypic fluctuation and robustness in response to host-parasite interactions.

Dataset Information

Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions.

Publications

Rewiring capsule production by CRISPRi-based genetic oscillators demonstrates a functional role of phenotypic variation in pneumococcal-host interactions.

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