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The neural and molecular mechanisms underlying food preference have been poorly understood. We previously showed that Bifidobacterium infantis (B. infantis), a well-known probiotic bacterium, extends the lifespan of Caenorhabditis elegans (C. elegans) compared with a standard food, Escherichia coli (E. coli) OP50. In this study, we characterized C. elegans behavior against B. infantis and examined the neural and molecular mechanisms governing that behavior. The majority of the wild-type animals were outside of the B. infantis lawn 10 min after transfer. Although worms did not prefer B. infantis compared to E. coli OP50, they preferred the B. infantis lawn over a lawn containing M9 buffer alone, in which there was no food. Mutant analyses suggested that leaving the B. infantis lawn required daf-16/FOXO. Isoform-specific mutant phenotypes suggested that daf-16 isoform b seemed to be associated with leaving. Genetic rescue experiments demonstrated that the function of daf-16b in AIY interneurons was involved in leaving the B. infantis lawn. The daf-18/PTEN mutants were also defective in leaving. In conclusion, C. elegans showed a low preference for B. infantis, and daf-16b in AIY interneurons and daf-18 had roles in leaving B. infantis.

Caenorhabditis auriculariae, which was morphologically described in 1999, was re-isolated from a Platydema mushroom-associated beetle. Based on the re-isolated materials, some morphological characteristics were re-examined and ascribed to the species. In addition, to clarify phylogenetic relationships with other Caenorhabditis species and biological features of the nematode, the whole genome was sequenced and assembled into 109.5 Mb with 16,279 predicted protein-coding genes. Molecular phylogenetic analyses based on ribosomal RNA and 269 single-copy genes revealed the species is closely related to C. sonorae and C. monodelphis placing them at the most basal clade of the genus. C. auriculariae has morphological characteristics clearly differed from those two species and harbours a number of species-specific gene families, indicating its usefulness as a new outgroup species for Caenorhabditis evolutionary studies. A comparison of carbohydrate-active enzyme (CAZy) repertoires in genomes, which we found useful to speculate about the lifestyle of Caenorhabditis nematodes, suggested that C. auriculariae likely has a life-cycle with tight-association with insects. Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [26292083, 26292178, 19H03212]; Ministry of the Environment, JapanMinistry of the Environment, Japan [4-1401]; JST CRESTJapan Science & Technology Agency (JST)Core Research for Evolutional Science and Technology (CREST) [JPMJCR18S7] We thank Noriko Shimoda, Atsuko Matsumoto and Akemi Yoshida for their technical assistance in culturing the nematodes, preparing the permanent mounts and sequencing. This study was supported, in part, by Grants-in-Aid for Scientific Research (B), nos. 26292083, 26292178 and 19H03212 from the Japan Society for the Promotion of Science, Environment Research and Technology Development Fund (4-1401) from the Ministry of the Environment, Japan and JST CREST Grant Number JPMJCR18S7. WOS:000634969500009 2-s2.0-85103355410 PubMed: 33762598

Accumulating studies have argued that the mitochondrial unfolded protein response (UPRmt) is a mitochondrial stress response that promotes longevity in model organisms. In the present study, we screened an off-patent drug library to identify compounds that activate UPRmt using a mitochondrial chaperone hsp-6::GFP reporter system in Caenorhabditis elegans. Metolazone, a diuretic primarily used to treat congestive heart failure and high blood pressure, was identified as a prominent hit as it upregulated hsp-6::GFP and not the endoplasmic reticulum chaperone hsp-4::GFP. Furthermore, metolazone specifically induced the expression of mitochondrial chaperones in the HeLa cell line. Metolazone also extended the lifespan of worms in a atfs-1 and ubl-5-dependent manner. Notably, metolazone failed to increase lifespan in worms with knocked-down nkcc-1. These results suggested that metolazone activates the UPRmt across species and prolongs the lifespan of C. elegans.

The membrane trafficking events that regulate unicellular tube formation and maintenance are not well understood. Here, using an RNAi screen, we identified the small GTPase ARF1 homolog ARF-1.2 as a regulator of excretory tube formation in Caenorhabditis elegans. RNAi-mediated knockdown and knockout of the arf-1.2 gene resulted in the formation of large intracellular vacuoles at the growth sites (varicosities) of the excretory canals. arf-1.2 mutant animals were sensitive to hyperosmotic conditions. arf-1.2 RNAi affected the localization of the anion transporter SULP-8, which is expressed in the basal plasma membrane of the excretory canals, but did not affect the expression of SULP-4, which is expressed in the apical membrane. The phenotype of arf-1.2 mutants was suppressed by mutation of the small Rho GTPase CDC-42, a regulator of apical/basal traffic balance. These results suggest that ARF-1.2 plays an essential role in basal membrane traffic to regulate the formation of the unicellular excretory tube.

Clostridium butyricum MIYAIRI 588 (CBM 588), one of the probiotic bacterial strains used for humans and domestic animals, has been reported to exert a variety of beneficial health effects. The effect of this probiotic on lifespan, however, is unknown. In the present study, we investigated the effect of CBM 588 on lifespan and multiple-stress resistance using Caenorhabditis elegans as a model animal. When adult C. elegans were fed a standard diet of Escherichia coli OP50 or CBM 588, the lifespan of the animals fed CBM 588 was significantly longer than that of animals fed OP50. In addition, the animals fed CBM588 exhibited higher locomotion at every age tested. Moreover, the worms fed CBM 588 were more resistant to certain stressors, including infections with pathogenic bacteria, UV irradiation, and the metal stressor Cu2+. CBM 588 failed to extend the lifespan of the daf-2/insulin-like receptor, daf-16/FOXO and skn-1/Nrf2 mutants. In conclusion, CBM 588 extends the lifespan of C. elegans probably through regulation of the insulin/IGF-1 signaling (IIS) pathway and the Nrf2 transcription factor, and CBM 588 improves resistance to several stressors in C. elegans.