Molecular causes of an evolutionary shift along the parasitism-mutualism continuum in a bacterial symbiont
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ABSTRACT:
PROVIDER: PRJNA574613 | ENA |
REPOSITORIES: ENA
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Project description:Symbiosis is a ubiquitous phenomenon in nature, and these inter-species interactions have a massive impact on organisms, shaping the world around us today. The relationship between the partners in microbial symbioses have been described as existing along a parasitism-mutualism continuum, and the dynamics of this continuum are dependent upon numerous genotypic and environmental factors. Theoretical and experimental studies show that vertical transmission (VT) leads to the evolution of mutualistic traits, whereas horizontal transmission (HT) facilitates the emergence of parasitic features. However, these studies focused on phenotypic data, and we know little about underlying molecular changes at the genomic level. Here we show that a dramatic shift in the frequency of genetic variants, coupled with major changes in gene expression, allow an obligate intracellular bacterial symbiont to alter its position in the mutualism-parasitism continuum depending on the mode of between-host transmission. We found that increased virulence in horizontally transmitted chlamydiae residing in amoebae was a result of processes occurring at the infectious stage of the chlamydia’s developmental cycle. Specifically, genes involved in energy production required for extracellular survival as well as the type III secretion system (T3SS) - the symbiont’s primary virulence mechanism - were significantly upregulated. Our results identify the genomic and transcriptomic dynamics sufficient to favor parasitic or mutualistic strategies.
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Project description:This SuperSeries is composed of the SubSeries listed below. Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247691 | GEO
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
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Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247689 | GEO
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247688 | GEO
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247687 | GEO
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247686 | GEO
Project description:Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance. Beyond genetic mutations, recent research has shed light on the role of non-genetic plasticity in transient drug tolerance and the acquisition of stable resistance. However, the dynamics of cell state transitions occurring in the adaptation to cancer therapies remain elusive and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell state transitions accompanied by a progressive increase in cell fitness, which we denote the 'resistance continuum'. This cellular adaptation involves a step-wise assembly of gene expression programs and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that EMT/stemness programs, often considered as a proxy for phenotypic plasticity, enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify an acquisition of metabolic dependencies, exposing vulnerabilities that can be potentially exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell state transitions.
2024-05-22 | GSE247685 | GEO