Intergenerational pathogen-induced diapause in C. elegans is modulated by mir-243

AbstractThe interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNAi machinery, suggesting the involvement of sRNAs as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small non-coding RNAs, we found that mir-243-3p is the only transcript continuously upregulated in animals exposed to both, P. aeruginosa or S. enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small non-coding RNA in the intergenerational defensive response against pathogenic bacteria and inter-kingdom communication.ImportancePersistent infection of the bacterivore nematode C. elegans with bacteria such as P. aeruginosa and S. enterica makes the worm diapause or hibernate. By doing this, the worm closes its mouth avoiding infection. This response takes two generations to be implemented. In this work, we looked for genes expressed upon infection that could mediate the worm diapause triggered by pathogens. We identify mir-243-3p as the only transcript commonly upregulated when animals feed on P. aeruginosa and S. enterica for two consecutive generations. Moreover, we demonstrate that mir-243-3p is required for pathogen-induced dauer formation, a new function that has not been previously described for this miRNA. We also find that the transcriptional activators DAF-16, PQM-1 and CRH-2 are necessary for the expression of mir-243 under pathogenesis. Here we establish a relationship between a small RNA and a developmental change that ensures the survival of a percentage of the progeny.

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Intergenerational Pathogen-Induced Diapause in Caenorhabditis elegans Is Modulated by mir-243

mBio ◽

10.1128/mbio.01950-20 ◽

2020 ◽

Vol 11 (5) ◽

Author(s):

Carolaing Gabaldón ◽

Marcela Legüe ◽

M. Fernanda Palominos ◽

Lidia Verdugo ◽

Florence Gutzwiller ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Noncoding Rna ◽

Pathogenic Bacteria ◽

Developmental Change ◽

Differential Expression Analysis ◽

Phenotypic Analysis ◽

Content Type ◽

C Elegans ◽

Two Generations ◽

Dauer Formation

ABSTRACT The interaction and communication between bacteria and their hosts modulate many aspects of animal physiology and behavior. Dauer entry as a response to chronic exposure to pathogenic bacteria in Caenorhabditis elegans is an example of a dramatic survival response. This response is dependent on the RNA interference (RNAi) machinery, suggesting the involvement of small RNAs (sRNAs) as effectors. Interestingly, dauer formation occurs after two generations of interaction with two unrelated moderately pathogenic bacteria. Therefore, we sought to discover the identity of C. elegans RNAs involved in pathogen-induced diapause. Using transcriptomics and differential expression analysis of coding and long and small noncoding RNAs, we found that mir-243-3p (the mature form of mir-243) is the only transcript continuously upregulated in animals exposed to both Pseudomonas aeruginosa and Salmonella enterica for two generations. Phenotypic analysis of mutants showed that mir-243 is required for dauer formation under pathogenesis but not under starvation. Moreover, DAF-16, a master regulator of defensive responses in the animal and required for dauer formation was found to be necessary for mir-243 expression. This work highlights the role of a small noncoding RNA in the intergenerational defensive response against pathogenic bacteria and interkingdom communication. IMPORTANCE Persistent infection of the bacterivore nematode C. elegans with bacteria such as P. aeruginosa and S. enterica makes the worm diapause or hibernate. By doing this, the worm closes its mouth, avoiding infection. This response takes two generations to be implemented. In this work, we looked for genes expressed upon infection that could mediate the worm diapause triggered by pathogens. We identify mir-243-3p as the only transcript commonly upregulated when animals feed on P. aeruginosa and S. enterica for two consecutive generations. Moreover, we demonstrate that mir-243-3p is required for pathogen-induced dauer formation, a new function that has not been previously described for this microRNA (miRNA). We also find that the transcriptional activators DAF-16, PQM-1, and CRH-2 are necessary for the expression of mir-243 under pathogenesis. Here we establish a relationship between a small RNA and a developmental change that ensures the survival of a percentage of the progeny.

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

mBio ◽

10.1128/mbio.01234-17 ◽

2017 ◽

Vol 8 (5) ◽

Cited By ~ 25

Author(s):

M. Fernanda Palominos ◽

Lidia Verdugo ◽

Carolaing Gabaldon ◽

Bernardo Pollak ◽

Javiera Ortíz-Severín ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Behavioral Change ◽

Pathogenic Bacteria ◽

Behavioral Changes ◽

Survival Strategies ◽

Information Encoding ◽

C Elegans ◽

Two Generations ◽

And Behavior ◽

Dauer Larvae

ABSTRACT The dynamic response of organisms exposed to environmental pathogens determines their survival or demise, and the outcome of this interaction depends on the host’s susceptibility and pathogen-dependent virulence factors. The transmission of acquired information about the nature of a pathogen to progeny may ensure effective defensive strategies for the progeny’s survival in adverse environments. Environmental RNA interference (RNAi) is a systemic and heritable mechanism and has recently been linked to antibacterial and antifungal defenses in both plants and animals. Here, we report that the second generation of Caenorhabditis elegans living on pathogenic bacteria can avoid bacterial infection by entering diapause in an RNAi pathway-dependent mechanism. Furthermore, we demonstrate that the information encoding this survival strategy is transgenerationally transmitted to the progeny via the maternal germ line. IMPORTANCE Bacteria vastly influence physiology and behavior, and yet, the specific mechanisms by which they cause behavioral changes in hosts are not known. We use C. elegans as a host and the bacteria they eat to understand how microbes trigger a behavioral change that helps animals to survive. We found that animals faced with an infection for two generations could enter a hibernationlike state, arresting development by forming dauer larvae. Dauers have closed mouths and effectively avoid infection. Animals accumulate information that is transgenerationally transmitted to the next generations to form dauers. This work gives insight on how bacteria communicate in noncanonical ways with their hosts, resulting in long-lasting effects providing survival strategies to the community. IMPORTANCE Bacteria vastly influence physiology and behavior, and yet, the specific mechanisms by which they cause behavioral changes in hosts are not known. We use C. elegans as a host and the bacteria they eat to understand how microbes trigger a behavioral change that helps animals to survive. We found that animals faced with an infection for two generations could enter a hibernationlike state, arresting development by forming dauer larvae. Dauers have closed mouths and effectively avoid infection. Animals accumulate information that is transgenerationally transmitted to the next generations to form dauers. This work gives insight on how bacteria communicate in noncanonical ways with their hosts, resulting in long-lasting effects providing survival strategies to the community.

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Isolation and Characterization of Strain Exiguobacterium sp. KRL4, a Producer of Bioactive Secondary Metabolites from a Tibetan Glacier

Microorganisms ◽

10.3390/microorganisms9050890 ◽

2021 ◽

Vol 9 (5) ◽

pp. 890

Author(s):

Pietro Tedesco ◽

Fortunato Palma Esposito ◽

Antonio Masino ◽

Giovanni Andrea Vitale ◽

Emiliana Tortorella ◽

...

Keyword(s):

Phenotypic Analysis ◽

Biological Assays ◽

C Elegans ◽

Isolation And Characterization ◽

Wide Range ◽

Protein Encoding ◽

Nematocidal Activity ◽

Extremophilic Microorganisms ◽

Unique Source

Extremophilic microorganisms represent a unique source of novel natural products. Among them, cold adapted bacteria and particularly alpine microorganisms are still underexplored. Here, we describe the isolation and characterization of a novel Gram-positive, aerobic rod-shaped alpine bacterium (KRL4), isolated from sediments from the Karuola glacier in Tibet, China. Complete phenotypic analysis was performed revealing the great adaptability of the strain to a wide range of temperatures (5–40 °C), pHs (5.5–8.5), and salinities (0–15% w/v NaCl). Genome sequencing identified KRL4 as a member of the placeholder genus Exiguobacterium_A and annotation revealed that only half of the protein-encoding genes (1522 of 3079) could be assigned a putative function. An analysis of the secondary metabolite clusters revealed the presence of two uncharacterized phytoene synthase containing pathways and a novel siderophore pathway. Biological assays confirmed that the strain produces molecules with antioxidant and siderophore activities. Furthermore, intracellular extracts showed nematocidal activity towards C. elegans, suggesting that strain KRL4 is a source of anthelmintic compounds.

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Hydrogen Sulfide Increases Hypoxia-inducible Factor-1 Activity Independently of von Hippel–Lindau Tumor Suppressor-1 inC. elegans

Molecular Biology of the Cell ◽

10.1091/mbc.e09-03-0199 ◽

2010 ◽

Vol 21 (1) ◽

pp. 212-217 ◽

Cited By ~ 58

Author(s):

Mark W. Budde ◽

Mark B. Roth

Keyword(s):

Hydrogen Sulfide ◽

Tumor Suppressor ◽

Environmental Changes ◽

Hypoxia Inducible Factor ◽

Low Oxygen ◽

Animal Cells ◽

Von Hippel Lindau ◽

C Elegans ◽

Reporter Activity ◽

And Behavior

Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor hypoxia-inducible factor (HIF)-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here, we show that Caenorhabditis elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis, whereas hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H2S. Exposure to H2S results in HIF-1 nuclear localization and transcription of HIF-1 targets. The effects of H2S on HIF-1 reporter activity are independent of von Hippel–Lindau tumor suppressor (VHL)-1, whereas VHL-1 is required for hypoxic regulation of HIF-1 reporter activity. Because H2S is naturally produced by animal cells, our results suggest that endogenous H2S may influence HIF-1 activity.

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Deficiency of innate immunity against P. aeruginosa enhances behavioral avoidance via the HECW-1/NPR-1 module in C. elegans

Infection and Immunity ◽

10.1128/iai.00067-21 ◽

2021 ◽

Author(s):

Hua Bai ◽

Wei Zou ◽

Wenhui Zhou ◽

Keqin Zhang ◽

Xiaowei Huang

Keyword(s):

Innate Immunity ◽

Pathogenic Bacteria ◽

Immune Gene ◽

Biological Processes ◽

Defensive Strategy ◽

C Elegans ◽

Defensive Strategies ◽

Behavioral Avoidance ◽

Neuropeptide Y Receptor ◽

G Protein Coupled

To antagonize infection of pathogenic bacteria in soil and confer increased survival, Caenorhabditis elegans employs innate immunity and behavioral avoidance synchronously as the two main defensive strategies. Although both biological processes and their individual signaling pathways have been partially elucidated, knowledge of their interrelationship remains limited. The current study reveals that deficiency of innate immunity triggered by mutation of the classic immune gene pmk-1 promotes avoidance behavior in C. elegans ; and vice versa. Restoration of pmk-1 expression using the tissue-specific promoters suggested that the functional loss of both intestinal and neuronal pmk-1 is necessary for the enhanced avoidance. Additionally, PMK-1 co-localized with the E3 ubiquitin ligase HECW-1 in OLL neurons and regulated the expressional level of the latter, which consequently affected the production of NPR-1, a G-protein-coupled receptor homologous to the mammalian neuropeptide Y receptor, in RMG neurons in a non-cell-autonomous manner. Collectively, our study illustrates, once the innate immunity is impaired when C. elegans antagonizes bacterial infection, the other defensive strategy of behavioral avoidance can be enhanced accordingly via the HECW-1/NPR-1 module, suggesting that GPCRs in neural circuits may receive the inputs from immune system and integrate those two systems for better adapting to the real-time status.

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Structural characterization of acyl-CoA oxidases reveals a direct link between pheromone biosynthesis and metabolic state in Caenorhabditis elegans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608262113 ◽

2016 ◽

Vol 113 (36) ◽

pp. 10055-10060 ◽

Cited By ~ 19

Author(s):

Xinxing Zhang ◽

Kunhua Li ◽

Rachel A. Jones ◽

Steven D. Bruner ◽

Rebecca A. Butcher

Keyword(s):

Caenorhabditis Elegans ◽

Nematode Species ◽

Binding Pocket ◽

Pheromone Biosynthesis ◽

Atp Binding ◽

Metabolic State ◽

C Elegans ◽

Acyl Coa Oxidase ◽

Key Residues ◽

And Behavior

Caenorhabditis elegans secretes ascarosides as pheromones to communicate with other worms and to coordinate the development and behavior of the population. Peroxisomal β-oxidation cycles shorten the side chains of ascaroside precursors to produce the short-chain ascaroside pheromones. Acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, have different side chain-length specificities and enable C. elegans to regulate the production of specific ascaroside pheromones. Here, we determine the crystal structure of the acyl-CoA oxidase 1 (ACOX-1) homodimer and the ACOX-2 homodimer bound to its substrate. Our results provide a molecular basis for the substrate specificities of the acyl-CoA oxidases and reveal why some of these enzymes have a very broad substrate range, whereas others are quite specific. Our results also enable predictions to be made for the roles of uncharacterized acyl-CoA oxidases in C. elegans and in other nematode species. Remarkably, we show that most of the C. elegans acyl-CoA oxidases that participate in ascaroside biosynthesis contain a conserved ATP-binding pocket that lies at the dimer interface, and we identify key residues in this binding pocket. ATP binding induces a structural change that is associated with tighter binding of the FAD cofactor. Mutations that disrupt ATP binding reduce FAD binding and reduce enzyme activity. Thus, ATP may serve as a regulator of acyl-CoA oxidase activity, thereby directly linking ascaroside biosynthesis to ATP concentration and metabolic state.

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Bacteriophages: from isolation to application

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210426092002 ◽

2021 ◽

Vol 22 ◽

Author(s):

Abdallah S. Abdelsattar ◽

Alyaa Dawoud ◽

Salsabil Makky ◽

Rana Nofal ◽

Ramy K. Aziz ◽

...

Keyword(s):

Food Industry ◽

Pathogenic Bacteria ◽

Phage Genome ◽

Morphological Structure ◽

High Specificity ◽

Potential Alternative ◽

And Behavior ◽

Phage Isolation ◽

Different Levels ◽

Selection Of

: Bacteriophages are considered as a potential alternative to fight pathogenic bacteria during the antibiotic resistance era. With their high specificity, they are being widely used in various applications: medicine, food industry, agriculture, animal farms, biotechnology, diagnosis, etc. Many techniques have been designed by different researchers for phage isolation, purification, and amplification, each of which has strengths and weaknesses. However, all aim at having a reasonably pure phage sample that can be further characterized. Phages can be characterized based on their physiological, morphological or inactivation tests. Microscopy, in particular, has opened a wide gate not only for visualizing phage morphological structure, but also for monitoring biochemistry and behavior. Meanwhile, computational analysis of phage genomes provides more details about phage history, lifestyle, and potential for toxigenic or lysogenic conversion, which translate to safety in biocontrol and phage therapy applications. This review summarizes phage application pipelines at different levels and addresses specific restrictions and knowledge gaps in the field. Recently developed computational approaches, which are used in phage genome analysis, are critically assessed. We hope that this assessment provides researchers with useful insights for selection of suitable approaches for Phage-related research aims and applications.

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Sonic Stimulation and Low Power Microwave Radiation Can Modulate Bacterial Virulence Towards Caenorhabditis elegans

Anti-Infective Agents ◽

10.2174/2211352516666181102150049 ◽

2019 ◽

Vol 17 (2) ◽

pp. 150-162

Author(s):

Priya Patel ◽

Hiteshi Patel ◽

Dhara Vekariya ◽

Chinmayi Joshi ◽

Pooja Patel ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Microwave Radiation ◽

Pathogenic Bacteria ◽

Bacterial Virulence ◽

Therapeutic Approaches ◽

Microwave Exposure ◽

C Elegans ◽

Sonic Treatment ◽

Global Threat ◽

Sound Treatment

<P>Background: In view of the global threat of antimicrobial resistance, novel alternative approaches to deal with infectious bacteria are warranted, in addition to the conventional invasive therapeutic approaches. Objective: This study aimed at investigating whether exposure to sonic stimulation or microwave radiation can affect virulence of pathogenic bacteria toward the model nematode host Caenorhabditis elegans. Methods: Caenorhabditis elegans worms infected with different pathogenic bacteria were subjected to sonic treatment to investigate whether such sound treatment can exert any therapeutic effect on the infected worms. Virulence of microwave exposed bacteria was also assessed using this nematode host. Results: Sound corresponding to 400 Hz, and the divine sound ‘Om’ conferred protective effect on C. elegans in face of bacterial infection, particularly that caused by Serratia marcescens or Staphylococcus aureus. The observed effect seemed to occur due to influence of sound on bacteria, and not on the worm. Additionally, effect of microwave exposure on bacterial virulence was also investigated, wherein microwave exposure could reduce virulence of S. aureus towards C. elegans. Conclusion: Sonic stimulation/ microwave exposure was demonstrated to be capable of modulating bacterial virulence.</P>

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