-
[
International Worm Meeting,
2019]
Mitochondrial abundance and function are key regulators of lifespan and healthspan in organisms as diverse as the nematode C. elegans and humans. Mitochondrial biogenesis and the selective removal of dysfunctional mitochondria via mitophagy are opposing processes that tightly control both the organelle number and homeostasis. Despite the fact that mitophagy has been extensively studied, still little is known about mitochondrial biogenesis. Due to their semi-autonomous nature, mitochondria rely on the expression of both the nuclear and the mitochondrial genome for their biogenesis. The transcription factor SKN-1 and the signaling module AAK-2 are known to promote mitochondrial biogenesis through transcriptional control processes. However, the post-transcriptional mechanisms that regulate nuclear encoded and mitochondrial-targeted transcript (NEMTT) expression, required for the organelle biogenesis, remain elusive. To address this issue in vivo, we implement a wide range of genetic tools and advanced microscopy techniques. We find that cytoplasmic RNA processing components of the decapping and the CCR-4/NOT complex both physically and functionally associate with mitochondria to regulate the organelle abundance and function. Specifically, we uncover a pivotal role of mRNA metabolism factors in the regulation of local translation of NEMTTs during ageing. Our data underscore the importance of post-transcriptional control of NEMTT expression for lifespan and stress resistance in C. elegans. Given the high conservation of the decapping and CCR-4/NOT complex components, this mechanism is probably relevant to pathologies involving mitochondrial abnormalities in humans.
-
[
EMBO J,
2023]
Mitochondria are central regulators of healthspan and lifespan, yet the intricate choreography of multiple, tightly controlled steps regulating mitochondrial biogenesis remains poorly understood. Here, we uncover a pivotal role for specific elements of the 5'-3' mRNA degradation pathway in the regulation of mitochondrial abundance and function. We find that the mRNA degradation and the poly-A tail deadenylase CCR4-NOT complexes form distinct foci in somatic Caenorhabditis elegans cells that physically and functionally associate with mitochondria. Components of these two multi-subunit complexes bind transcripts of nuclear-encoded mitochondria-targeted proteins to regulate mitochondrial biogenesis during ageing in an opposite manner. In addition, we show that balanced degradation and storage of mitochondria-targeted protein mRNAs are critical for mitochondrial homeostasis, stress resistance and longevity. Our findings reveal a multifaceted role of mRNA metabolism in mitochondrial biogenesis and show that fine-tuning of mRNA turnover and local translation control mitochondrial abundance and promote longevity in response to stress and during ageing.
-
[
International Worm Meeting,
2017]
Mitochondrial metabolism is crucial for the modulation and maintenance of cellular homeostasis. Mitochondrial number and functionality largely determine intracellular ATP, Ca2+ and ROS levels, which in turn regulate cellular redox state, and may initiate signaling cascades involved in cell death, ageing and disease. Various stressors affect mitochondrial function and trigger retrograde and anterograde responses that enable cells to adapt their metabolism under stress conditions. Cellular metabolic state, upon stress and during ageing, is also determined by the fraction of mRNAs undergoing translation, storage or degradation. Recent studies have shown that tight control of mRNA turnover mechanisms is needed for normal cell physiology, highlighting their global regulatory capacity. The significance of these mechanisms is further supported by their evolutionary conservation from lower to higher eukaryotes. Emerging findings indicating that mitochondrial metabolism is altered in response to cytoplasmic stress, prompted us to examine the functional crosstalk between the two pathways. We are currently investigating this interplay in vivo by combining state of the art optical imaging methodologies with the power of genetic analysis in C. elegans. We find that reduced expression of key mRNA metabolism components causes alterations in mitochondrial morphology and function. Downregulation of the decapping protein DCAP-2 perturbs mitochondrial content and network integrity. In addition, mitochondrial impairment caused by pharmacological treatment, either with paraquat or CCCP, alters the expression of mRNA metabolism factors. Our results indicate that the two mechanisms are coupled and regulate energy metabolism, stress resistance and longevity. Elucidation of this complex association is important towards understanding how metabolic alterations trigger (re)adjustments in mitochondrial physiology that ultimately influence healthspan and ageing.
-
[
Genes (Basel),
2018]
<i>Caenorhabditis</i><i>elegans</i> is a valuable tool as an infection model toward the study of <i>Candida</i> species. In this work, we endeavored to develop a <i>C</i>. <i>elegans</i>-<i>Candida</i><i>parapsilosis</i> infection model by using the fungi as a food source. Three species of the C. parapsilosis complex (<i>C.</i><i>parapsilosis</i> (<i>sensu</i><i>stricto</i>), <i>Candida</i><i>orthopsilosis</i> and <i>Candida</i><i>metapsilosis</i>) caused infection resulting in <i>C. elegans</i> killing. All three strains that comprised the complex significantly diminished the nematode lifespan, indicating the virulence of the pathogens against the host. The infection process included invasion of the intestine and vulva which resulted in organ protrusion and hyphae formation. Importantly, hyphae formation at the vulva opening was not previously reported in <i>C</i>. <i>elegans</i>-<i>Candida</i> infections. Fungal infected worms in the liquid assay were susceptible to fluconazole and caspofungin and could be found to mount an immune response mediated through increased expression of <i>cnc</i>-<i>4</i>, <i>cnc</i>-<i>7</i>, and <i>fipr</i><i>-</i><i>22</i>/<i>23</i>. Overall, the <i>C</i>. <i>elegans</i>-<i>C</i>. <i>parapsilosis</i> infection model can be used to model <i>C</i>. <i>parapsilosis</i> host-pathogen interactions.
-
[
Front Cell Infect Microbiol,
2021]
The yeast <i>Candida albicans</i> exhibits multiple morphologies dependent on environmental cues. <i>Candida albicans</i> biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between <i>C. albicans</i> and the bacterium, <i>Pseudomonas aeruginosa</i>, is antagonistic <i>in vitro, with P. aeruginosa</i> repressing the yeast-to-hyphal switch in <i>C. albicans</i>. Previous transcriptional analysis of <i>C. albicans</i> in polymicrobial biofilms with <i>P. aeruginosa</i> revealed upregulation of genes involved in regulation of morphology and biofilm formation, including <i>SET3</i>, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of <i>SET3</i> in the interaction between <i>C. albicans</i> and <i>P. aeruginosa</i>, both <i>in vitro</i> and <i>in vivo.</i> We found that <i>SET3</i> may influence early biofilm formation by <i>C. albicans</i> and the interaction between <i>C. albicans</i> and <i>P. aeruginosa</i>. In addition, although deletion of <i>SET3</i> did not alter the morphology of <i>C. albicans</i> in the presence of <i>P. aeruginosa</i>, it did cause a reduction in virulence in a <i>Caenorhabditis elegans</i> infection model, even in the presence of <i>P. aeruginosa.</i>
-
[
Oxid Med Cell Longev,
2020]
Naringin is a dihydroflavonoid, which is rich in several plant species used for herbal medicine. It has a wide range of biological activities, including antineoplastic, anti-inflammatory, antiphotoaging, and antioxidative activities. So it would be interesting to know if naringin has an effect on aging and aging-related diseases. We examined the effect of naringin on the aging of <i>Caenorhabditis elegans</i> (<i>C</i>. <i>elegans</i>). Our results showed that naringin could extend the lifespan of <i>C</i>. <i>elegans</i>. Moreover, naringin could also increase the thermal and oxidative stress tolerance, reduce the accumulation of lipofuscin, and delay the progress of aging-related diseases in <i>C</i>. <i>elegans</i> models of AD and PD. Naringin could not significantly extend the lifespan of long-lived mutants from genes in insulin/IGF-1 signaling (IIS) and nutrient-sensing pathways, such as <i>daf</i>-<i>2</i>, <i>akt</i>-<i>2</i>, <i>akt</i>-<i>1</i>, <i>eat</i>-<i>2</i>, <i>sir</i>-<i>2</i>.<i>1</i>, and <i>rsks</i>-<i>1</i>. Naringin treatment prolonged the lifespan of long-lived <i>glp</i>-<i>1</i> mutants, which have decreased reproductive stem cells. Naringin could not extend the lifespan of a null mutant of the fox-head transcription factor DAF-16. Moreover, naringin could increase the mRNA expression of genes regulated by <i>daf</i>-<i>16</i> and itself. In conclusion, we show that a natural product naringin could extend the lifespan of <i>C</i>. <i>elegans</i> and delay the progression of aging-related diseases in <i>C</i>. <i>elegans</i> models via DAF-16.
-
Chen YW, Chen PL, Su YC, Li CW, Lin YT, Lee NY, Shu CY, Ko WC, Li MC, Su SL, Wu CJ
[
Appl Environ Microbiol,
2019]
The present study aimed to isolate <i>Aeromonas</i> from fish sold in the markets as well as in sushi and seafood shops and compare their virulence factors and antimicrobial characteristics with those of clinical isolates. Among the 128 fish isolates and 47 clinical isolates, <i>A. caviae</i>, <i>A. dhakensis</i>, and <i>A. veronii</i> were the principal species. <i>A. dhakensis</i> isolates carried at least 5 virulence genes, more than other <i>Aeromonas</i> species. The predominant genotype of virulence genes was <i>hlyA/lip/alt/col/el</i> in both <i>A. dhakensis</i> and <i>A. hydrophila</i> isolates, <i>alt/col/ela</i> in <i>A. caviae</i> isolates, and <i>act</i> in <i>A. veronii</i> isolates. <i>A. dhakensis</i>, <i>A. hydrophila</i>, and <i>A. veronii</i> isolates more often exhibited hemolytic and proteolytic activity and showed greater virulence than <i>A. caviae</i> in <i>Caenorhabditis elegans</i> and the C2C12 cell line. However, the link between the genotypes and phenotypes of the studied virulence genes in <i>Aeromonas</i> species is not evident. Among the four major clinical <i>Aeromonas</i> species, nearly all (99.0%) <i>A. dhakensis</i>, <i>A. hydrophila</i>, and <i>A. veronii</i> isolates harbored <i>bla</i><sub>CphA</sub>, which encodes a carbapenemase, but only a minority (6.7%, 7/104) were nonsusceptible to carbapenem. Regarding AmpC -lactamase genes, <i>bla</i><sub>AQU-1</sub> was exclusively found in <i>A. dhakensis</i> isolates and <i>bla</i><sub>MOX3</sub> only in <i>A. caviae</i> isolates, but only 7.6% (6) of the 79 <i>Aeromonas</i> isolates carrying <i>bla</i><sub>AQU-1</sub> or <i>bla</i><sub>MOX3</sub> exhibited a cefotaxime resistance phenotype. In conclusion, fish <i>Aeromonas</i> isolates carry a variety of combinations of virulence and B-lactamase resistance genes and exhibit virulence phenotypes and antimicrobial resistance profiles similar to those of clinical isolates.<b>IMPORTANCE</b><i>Aeromonas</i> species can cause severe infections in immunocompromised individuals upon exposure to virulent pathogens in the environment, but the characteristics of environmental <i>Aeromonas</i> species remain unclear. Our study showed several pathogenic <i>Aeromonas</i> species possessing virulence traits and antimicrobial resistance similar to those of <i>Aeromonas</i> isolates causing clinical diseases were present in fish intended for human consumption in Tainan City.
-
[
Heliyon,
2019]
This study identified the endoparasites in Brown rat (<i>Rattus norvegicus)</i> during May to July 2017 in Grenada, West Indies. A total of 162 rats, 76 females and 86 males were trapped from St. George and St. David parishes in Grenada. The collected fecal samples were examined for parasitic eggs and/or oocysts using simple fecal flotation technique. Adult parasites found in the intestinal tract were examined for identification. The overall prevalence of intestinal parasites among rats was 79 %. Ten helminth species were recovered, several of which were reported for the first time in rodents in Grenada. The internal parasites consist of seven nematodes (<i>Angiostrongylus</i> spp., <i>Nippostrongylus braziliensis</i>, <i>Heterakis spumosa</i>, <i>Strongyloides ratti</i>, <i>Aspiculuris tetraptera</i>, <i>Syphacia</i> spp. and <i>Protospirura</i> spp.), one cestode (<i>Hymenolepsis diminuta</i>), one acanthocephalan (<i>Moniliformis moniliformis</i>) and one protozoa species (<i>Eimeria</i> spp.). The most prevalent zoonotic species were <i>Angiostrongylus</i> spp. (35.2%), <i>Hymenolepsis diminuta</i> (7.4%) and <i>Moniliformis moniliformis</i> (3.1%). Several nonzoonotic endoparasites; which included <i>Nippostrongylus braziliensis</i> (50.6%), <i>Heterakis spumosa</i> (15.4%), <i>Strongyloides ratti</i> (43.2%), <i>Aspiculuris tetraptera</i> (2.5%), <i>Syphacia</i> spp<i>.</i> (1.9%), <i>Protospirura</i> spp. (1.2%) and <i>Eimeria</i> spp. (4.7%) were also identified. The most prevalent parasites were <i>Nippostrongylus brasiliensis</i> (50.6%), <i>Strongyloides ratti</i> (43.2%) and <i>Angiostrongylus spp.</i> (35.2%). Co-infections occurred with up to six species per rat showing different combinations of parasitic infections.
-
[
MicroPubl Biol,
2023]
In mice, mutation of <i>brca1</i> results in embryonic lethality, which is partially suppressed by <i>53bp1</i> mutation. In contrast, mutation of the <i>C. elegans</i> BRCA1 ortholog, <i>
brc-1 ,</i> or its binding partner, <i>
brd-1</i> , lead to only mild embryonic lethality. We show that in <i>C. elegans</i> , <i>
brc-1</i> and <i>
brd-1</i> embryonic lethality is enhanced when <i>53bp1</i> ortholog, <i>
hsr-9</i> , is also mutated. This is not a consequence of activating <i>
polq-1</i> -dependent microhomology-mediated end joining, as <i>
polq-1</i> mutation does not suppress embryonic lethality of <i>
hsr-9 ;
brc-1</i> mutants. Together, these results suggest that BRC-1 - BRD-1 and HSR-9 function in parallel pathways and do not act antagonistically as in mammals.
-
Hirsch AM, Whitman WB, Gross E, Estrada-de Los Santos P, Simon MF, Briscoe L, Crook M, Shapiro N, Chavez-Ramirez B, Palmer M, Maluk M, Dos Reis Junior FB, Poole PS, Humm E, Beukes C, James EK, Khan N, Arrabit M, Lafos M, Venter SN, Steenkamp ET
[
Genes (Basel),
2018]
<i>Burkholderia</i> sensu lato is a large and complex group, containing pathogenic, phytopathogenic, symbiotic and non-symbiotic strains from a very wide range of environmental (soil, water, plants, fungi) and clinical (animal, human) habitats. Its taxonomy has been evaluated several times through the analysis of 16S rRNA sequences, concantenated 47 housekeeping gene sequences, and lately by genome sequences. Currently, the division of this group into <i>Burkholderia</i>, <i>Caballeronia, Paraburkholderia</i>, and <i>Robbsia</i> is strongly supported by genome analysis. These new genera broadly correspond to the various habitats/lifestyles of <i>Burkholderia</i> s.l., e.g., all the plant beneficial and environmental (PBE) strains are included in <i>Paraburkholderia</i> (which also includes all the N-fixing legume symbionts) and <i>Caballeronia</i>, while most of the human and animal pathogens are retained in <i>Burkholderia</i> sensu stricto. However, none of these genera can accommodate two important groups of species. One of these includes the closely related <i>Paraburkholderia rhizoxinica</i> and <i>Paraburkholderia endofungorum</i>, which are both symbionts of the fungal phytopathogen <i>Rhizopus microsporus</i>. The second group comprises the <i>Mimosa</i>-nodulating bacterium <i>Paraburkholderia symbiotica</i>, the phytopathogen <i>Paraburkholderia caryophylli</i>, and the soil bacteria <i>Burkholderia dabaoshanensis</i> and <i>Paraburkholderia soli</i>. In order to clarify their positions within <i>Burkholderia</i> sensu lato, a phylogenomic approach based on a maximum likelihood analysis of conserved genes from more than 100 <i>Burkholderia</i> sensu lato species was carried out. Additionally, the average nucleotide identity (ANI) and amino acid identity (AAI) were calculated. The data strongly supported the existence of two distinct and unique clades, which in fact sustain the description of two novel genera <i>Mycetohabitans</i> gen. nov. and <i>Trinickia</i> gen. nov. The newly proposed combinations are <i>Mycetohabitans endofungorum</i> comb. nov., <i>Mycetohabitans</i><i>rhizoxinica</i> comb. nov., <i>Trinickia caryophylli</i> comb. nov., <i>Trinickia</i><i>dabaoshanensis</i> comb. nov., <i>Trinickia soli</i> comb. nov., and <i>Trinickia</i><i>symbiotica</i> comb. nov. Given that the division between the genera that comprise <i>Burkholderia</i> s.l. in terms of their lifestyles is often complex, differential characteristics of the genomes of these new combinations were investigated. In addition, two important lifestyle-determining traits-diazotrophy and/or symbiotic nodulation, and pathogenesis-were analyzed in depth i.e., the phylogenetic positions of nitrogen fixation and nodulation genes in <i>Trinickia</i> via-a-vis other <i>Burkholderiaceae</i> were determined, and the possibility of pathogenesis in <i>Mycetohabitans</i> and <i>Trinickia</i> was tested by performing infection experiments on plants and the nematode <i>Caenorhabditis elegans</i>. It is concluded that (1) <i>T. symbiotica nif</i> and <i>nod</i> genes fit within the wider <i>Mimosa</i>-nodulating <i>Burkholderiaceae</i> but appear in separate clades and that <i>T. caryophylli</i><i>nif</i> genes are basal to the free-living <i>Burkholderia</i> s.l. strains, while with regard to pathogenesis (2) none of the <i>Mycetohabitans</i> and <i>Trinickia</i> strains tested are likely to be pathogenic, except for the known phytopathogen <i>T. caryophylli</i>.