Transgenerational Diapause as an Avoidance Strategy against Bacterial Pathogens in
            <i>Caenorhabditis elegans</i>

Palominos, M. Fernanda; Verdugo, Lidia; Gabaldon, Carolaing; Pollak, Bernardo; Ortíz-Severín, Javiera; Varas, Macarena; Chávez, Francisco P.; Calixto, Andrea

doi:10.1128/mbio.01234-17

Cited by 62 publications

(124 citation statements)

References 53 publications

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“…The process we have uncovered here is also distinct from responses to prolonged, multigenerational bacterial exposure that induce dauer formation (Palominos et al, 2017;Moore and Murphy, unpublished data) and infection adaptation (Burton et al, 2019). For example, when worms are forced to encounter pathogenic Pseudomonas continuously (>6 days) over multiple generations, eventually their progeny halt development at the alternative, prereproductive L3 larval stage known as dauer, undergoing extensive remodeling of their cuticle, mouths, and other tissues.…”

Section: The Physiological Relevance Of Small Rna-induced Pathogen Avmentioning

confidence: 85%

C. elegans“reads” bacterial non-coding RNAs to learn pathogenic avoidance

Kaletsky

Moore²,

Vrla³

et al. 2020

Preprint

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C. elegans is exposed to many different bacteria in its environment, and must distinguish pathogenic from nutritious bacterial food sources. Here, we show that a single exposure to purified small RNAs isolated from pathogenic Pseudomonas aeruginosa (PA14) is sufficient to induce pathogen avoidance, both in the treated animals and in four subsequent generations of progeny. The RNA interference and piRNA pathways, the germline, and the ASI neuron are required for bacterial small RNA-induced avoidance behavior and transgenerational inheritance. A single non-coding RNA, P11, is both necessary and sufficient to convey learned avoidance of PA14, and its C. elegans target, maco-1, is required for avoidance. A natural microbiome Pseudomonas isolate, GRb0427, can induce avoidance via its small RNAs, and the wild C. elegans strain JU1580 responds similarly to bacterial sRNA. Our results suggest that this ncRNA-dependent mechanism evolved to survey the worm's microbial environment, use this information to make appropriate behavioral decisions, and pass this information on to its progeny.

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Section: The Physiological Relevance Of Small Rna-induced Pathogen Avmentioning

confidence: 85%

C. elegans“reads” bacterial non-coding RNAs to learn pathogenic avoidance

Kaletsky

Moore²,

Vrla³

et al. 2020

Preprint

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“…To distinguish between these two possibilities, we fed mec-4d animals with UV-killed HT115 bacteria, the most protective among those tested, and scored the AVM integrity at 72 hours. Additionally, we also evaluated UV-killed P. aeruginosa PAO1, a mild pathogen that needs to be alive to colonize and induce long-term defensive responses in the animal [15]. In both cases, dead bacteria protected to the same extent as live bacteria (Fig 2A).…”

Section: Bacterial Components Promote Neuroprotectionmentioning

confidence: 99%

“…In C. elegans, some dietary bacteria-induced traits show heritable properties [15]. Therefore, we tested whether neuronal protection could be inherited.…”

Section: Early Exposure Of Animals To E Coli Ht115 Is Sufficient Formentioning

confidence: 99%

“…Both the animal and its bacterial diet are genetically tractable, making them suitable for individual gene and large-scale mutation analysis. This system has been instrumental in deciphering specific metabolites from gut bacteria that influence developmental rate, fertility and aging [13], and host factors mediating germline maintenance in response to a variety of bacterial diets [14] as well as defensive behavioral strategies against pathogens [15].…”

Section: Introductionmentioning

confidence: 99%

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Bacterially produced metabolites protect C. elegans neurons from degeneration

et al. 2020

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Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the mechanosensory abnormality protein 4 (MEC-4d) degenerin/epithelial Na + (DEG/ENaC) channel, which causes the progressive degeneration of the touch receptor neurons (TRNs). Using this model, our study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. Although degeneration of TRNs was steady and completed at adulthood in the strain routinely used for C. elegans maintenance (Escherichia coli OP50), it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and was not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of DAF-16 (ortholog of the FOXO family of transcription factors), a phenomenon previously reported to underlie neuroprotection caused by downregulation of the insulin receptor in this system. Moreover, a daf-16 loss-of-function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics, and metabolomics approaches pinpointed the neurotransmitter γ-aminobutyric acid (GABA) and lactate as metabolites differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full PLOS BIOLOGY PLOS Biology | https://doi.

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“…Both the animal and its bacterial diet are genetically tractable making them suitable for individual gene and large-scale mutation analysis. This system has been instrumental in deciphering specific metabolites from gut bacteria influencing developmental rate, fertility and ageing [13], and host factors mediating germline maintenance in response to a variety of bacterial diets [14] as well as defensive behavioral strategies against pathogens [15].…”

Section: Introductionmentioning

confidence: 99%

Bacterially produced GABA protects neurons from degeneration

Urrutia

García

Fuentes-Flores

et al. 2019

Preprint

Self Cite

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Caenorhabditis elegans and its cognate bacterial diet comprise a reliable, widespread model to study diet and microbiota effects on host physiology. Nonetheless, how diet influences the rate at which neurons die remains largely unknown. A number of models have been used in C. elegans as surrogates for neurodegeneration. One of these is a C. elegans strain expressing a neurotoxic allele of the MEC-4(d) DEG/ENaC channel which causes the progressive degeneration of the touch receptor neurons (TRNs). Using such model, this study evaluated the effect of various dietary bacteria on neurodegeneration dynamics. While degeneration of TRNs was steadily carried and completed at adulthood in the strain routinely used for C. elegans maintenance Escherichia coli OP50, it was significantly reduced in environmental and other laboratory bacterial strains. Strikingly, neuroprotection reached more than 40% in the E. coli HT115 strain. HT115 protection was long lasting well into old age of animals and not restricted to the TRNs. Small amounts of HT115 on OP50 bacteria as well as UV-killed HT115 were still sufficient to produce neuroprotection. Early growth of worms in HT115 protected neurons from degeneration during later growth in OP50. HT115 diet promoted the nuclear translocation of the DAF-16/FOXO transcription factor, a phenomenon previously reported to underlie neuroprotection caused by downregulation of the insulin receptor in this system. Moreover, a daf-16 loss of function mutation abolishes HT115-driven neuroprotection. Comparative genomics, transcriptomics and metabolomics approaches pinpointed the neurotransmitter γ -aminobutyric acid (GABA) as a metabolite differentially produced between E. coli HT115 and OP50. HT115 mutant lacking glutamate decarboxylase enzyme genes (gad), which catalyze the conversion of GABA from glutamate, lost the ability to produce GABA and also to stop neurodegeneration. Moreover, in situ GABA supplementation or heterologous expression of glutamate decarboxylase in E. coli OP50 conferred neuroprotective activity to this strain. Specific C. elegans GABA transporters and receptors were required for full HT115-mediated neuroprotection. Together, these results demonstrate that bacterially produced GABA exerts an effect of neuroprotection in the host, highlighting the role of neuroactive compounds of the diet in nervous system homeostasis.

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Transgenerational Diapause as an Avoidance Strategy against Bacterial Pathogens in Caenorhabditis elegans

Cited by 62 publications

References 53 publications

C. elegans“reads” bacterial non-coding RNAs to learn pathogenic avoidance

C. elegans“reads” bacterial non-coding RNAs to learn pathogenic avoidance

Bacterially produced metabolites protect C. elegans neurons from degeneration

Bacterially produced GABA protects neurons from degeneration

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