A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans

Khanna, Amit; Kumar, Jitendra; Vargas, Misha A.; Barrett, LaKisha; Katewa, Subhash D.; Li, Patrick; McCloskey, Tom; Sharma, Amit; Naudé, Nicole; Nelson, Christopher S.; Brem, Rachel B.; Killilea, David W.; Mooney, Sean D.; Gill, Matthew S.; Kapahi, Pankaj

doi:10.1038/srep38764

Cited by 20 publications

(18 citation statements)

References 68 publications

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“…Interesting directions for future research include testing the hypothesis that microbial methionine metabolism influences organismal life span. We note that this idea is speculative, as it has not been supported by screens for bacterial influence on Caenorhabditis elegans longevity (79,80), and the manipulation of dietary methionine or methionine metabolism genes does not necessarily lead to tradeoffs between longevity and reproduction (58,81,82). Regardless, these data provide key hypotheses to pursue and support a previous assertion that future work investigating the relationship between Drosophila flies, the microbiota, and life history tradeoffs is of interest (83).…”

Section: Discussionmentioning

confidence: 61%

Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance

Judd

Matthews

Hughes

et al. 2018

Appl Environ Microbiol

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Animal-associated microorganisms (microbiota) dramatically influence the nutritional and physiological traits of their hosts. To expand our understanding of such influences, we predicted bacterial genes that influence a quantitative animal trait by a comparative genomic approach, and we extended these predictions via mutant analysis. We focused on starvation resistance (SR). We first confirmed that SR responds to the microbiota by demonstrating that bacterium-free flies have greater SR than flies bearing a standard 5-species microbial community, and we extended this analysis by revealing the species-specific influences of 38 genome-sequenced bacterial species on SR. A subsequent metagenome-wide association analysis predicted bacterial genes with potential influence on SR, among which were significant enrichments in bacterial genes for the metabolism of sulfur-containing amino acids and B vitamins. Dietary supplementation experiments established that the addition of methionine, but not B vitamins, to the diets significantly lowered SR in a way that was additive, but not interactive, with the microbiota. A direct role for bacterial methionine metabolism genes in SR was subsequently confirmed by analysis of flies that were reared individually with distinct methionine cycle mutants. The correlated responses of SR to bacterial methionine metabolism mutants and dietary modification are consistent with the established finding that bacteria can influence fly phenotypes through dietary modification, although we do not provide explicit evidence of this conclusion. Taken together, this work reveals that SR is a microbiota-responsive trait, and specific bacterial genes underlie these influences. Extending descriptive studies of animal-associated microorganisms (microbiota) to define causal mechanistic bases for their influence on animal traits is an emerging imperative. In this study, we reveal that starvation resistance (SR), a model quantitative trait in animal genetics, responds to the presence and identity of the microbiota. Using a predictive analysis, we reveal that the amino acid methionine has a key influence on SR and show that bacterial methionine metabolism mutants alter normal patterns of SR in flies bearing the bacteria. Our data further suggest that these effects are additive, and we propose the untested hypothesis that, similar to bacterial effects on fruit fly triacylglyceride deposition, the bacterial influence may be through dietary modification. Together, these findings expand our understanding of the bacterial genetic basis for influence on a nutritionally relevant trait of a model animal host.

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Section: Discussionmentioning

confidence: 61%

Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance

Judd

Matthews

Hughes

et al. 2018

Appl Environ Microbiol

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“…Additionally, although differences in the levels of L-Trypophan (Trp) metabolites in B and K strains may contribute to food-dependent differences in reproductive output [ 86 ], Trp levels do not appear to account for food quality effects on longevity in rict-1 mutants [ 54 ]. Thus, the relevant differences in nutrient profiles of these food sources are likely to be complex [ 87 ], and may also include differences in lipopolysaccharide (LPS) structures of the outer membranes of these bacteria [ 88 ]. In the future, identification of the metabolites produced by these bacteria should yield insights into the differential regulation of phenotypes by different bacterial strains in C .…”

Section: Discussionmentioning

confidence: 99%

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans

et al. 2018

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Animals integrate external cues with information about internal conditions such as metabolic state to execute the appropriate behavioral and developmental decisions. Information about food quality and quantity is assessed by the intestine and transmitted to modulate neuronal functions via mechanisms that are not fully understood. The conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in response to cellular stressors and growth factors. Here we show that TORC2 coordinates larval development and adult behaviors in response to environmental cues and feeding state in the bacterivorous nematode C. elegans. During development, pheromone, bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 insulin-like peptide in sensory neurons to promote a binary decision between reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which together reflect bacterial-diet dependent feeding status, thus providing a mechanism for integration of food signals with external cues in the regulation of neuroendocrine gene expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated foraging behaviors via a PDF-2/PDFR-1 neuropeptide signaling-dependent pathway. We also demonstrate that genetic variation affects food-dependent larval and adult phenotypes, and identify quantitative trait loci (QTL) associated with these traits. Together, these results suggest that TORC2 acts as a hub for communication of feeding state information from the gut to the brain, thereby contributing to modulation of neuronal function by internal state.

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“…Additionally, although differences in the levels of L-Trypophan 382 (Trp) metabolites in B and K strains may contribute to food-dependent differences in 383 reproductive output (80), Trp levels do not appear to account for food quality effects on 384 longevity in rict-1 mutants (54). Thus, the relevant differences in nutrient profiles of 385 these food sources are likely to be complex (81). In the future, identification of the 386 metabolites produced by these bacteria should yield insights into the differential 387 regulation of phenotypes by different bacterial strains in C. elegans, as well as the roles 388 of these nutrients in activating TORC2 signaling.…”

Section: A Role For Intestinal Torc2 In Nutrient Sensing 359mentioning

confidence: 99%

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

O’Donnell

Chao

Kammenga

et al. 2017

Preprint

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1Animals integrate external cues with information about internal conditions such as 2 metabolic state to execute the appropriate behavioral and developmental decisions. 3Information about food quality and quantity is assessed by the intestine and transmitted to 4 modulate neuronal functions via mechanisms that are not fully understood. The 5 conserved Target of Rapamycin complex 2 (TORC2) controls multiple processes in 6 response to cellular stressors and growth factors. Here we show that TORC2 coordinates 7 larval development and adult behaviors in response to environmental cues and feeding 8 state in the bacterivorous nematode C. elegans. During development, pheromone, 9 bacterial food, and temperature regulate expression of the daf-7 TGF-β and daf-28 10 insulin-like peptide in sensory neurons to promote a binary decision between 11 reproductive growth and entry into the alternate dauer larval stage. We find that TORC2 12 acts in the intestine to regulate neuronal expression of both daf-7 and daf-28, which 13 together reflect bacterial-diet dependent feeding status, thus providing a mechanism for 14 integration of food signals with external cues in the regulation of neuroendocrine gene 15 expression. In the adult, TORC2 similarly acts in the intestine to modulate food-regulated 16 foraging behaviors via the PDFR-1 neuropeptide receptor. We also demonstrate that 17 genetic variation affects food-dependent larval and adult phenotypes, and identify 18 quantitative trait loci (QTL) associated with these traits. Together, these results suggest 19 that TORC2 acts as a hub for communication of feeding state information from the gut to 20 the brain, thereby contributing to modulation of neuronal function by internal state. 21

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A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans

Cited by 20 publications

References 68 publications

Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance

Bacterial Methionine Metabolism Genes Influence Drosophila melanogaster Starvation Resistance

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity in C. elegans

Rictor/TORC2 mediates gut-to-brain signaling in the regulation of phenotypic plasticity inC. elegans

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