Displaying publications 21 - 40 of 41 in total

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  1. Lee WT, Tan BK, Eng SA, Yuen GC, Chan KL, Sim YK, et al.
    Food Funct, 2019 Sep 01;10(9):5759-5767.
    PMID: 31453615 DOI: 10.1039/c9fo01357a
    A strategy to circumvent the problem of multidrug resistant pathogens is the discovery of anti-infectives targeting bacterial virulence or host immunity. Black sea cucumber (Holothuria atra) is a tropical sea cucumber species traditionally consumed as a remedy for many ailments. There is a paucity of knowledge on the anti-infective capacity of H. atra and the underlying mechanisms involved. The objective of this study is to utilize the Caenorhabditis elegans-P. aeruginosa infection model to elucidate the anti-infective properties of H. atra. A bioactive H. atra extract and subsequently its fraction were shown to have the capability of promoting the survival of C. elegans during a customarily lethal P. aeruginosa infection. The same entities also attenuate the production of elastase, protease, pyocyanin and biofilm in P. aeruginosa. The treatment of infected transgenic lys-7::GFP worms with this H. atra fraction restores the repressed expression of the defense enzyme lys-7, indicating an improved host immunity. QTOF-LCMS analysis revealed the presence of aspidospermatidine, an indole alkaloid, and inosine in this fraction. Collectively, our findings show that H. atra possesses anti-infective properties against P. aeruginosa infection, by inhibiting pathogen virulence and, eventually, reinstating host lys-7 expression.
    Matched MeSH terms: Caenorhabditis elegans/drug effects; Caenorhabditis elegans/genetics; Caenorhabditis elegans/immunology; Caenorhabditis elegans/microbiology*
  2. Khoo CH, Sim JH, Salleh NA, Cheah YK
    Antonie Van Leeuwenhoek, 2015 Jan;107(1):23-37.
    PMID: 25312847 DOI: 10.1007/s10482-014-0300-7
    Salmonella is an important food-borne pathogen causing disease in humans and animals worldwide. Salmonellosis may be caused by any one of over 2,500 serovars of Salmonella. Nonetheless, Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Agona are the second most prevalent serovars isolated from humans and livestock products respectively. Limited knowledge is available about the virulence mechanisms responsible for diarrheal disease caused by them. To investigate the contribution of sopB, sopD and pipD as virulence factors in intracellular infections and the uniqueness of these bacteria becoming far more prevalent than other serovars, the infection model of Caenorhabditis elegans and phenotypic microarray were used to characterize their mutants. The strains containing the mutation in sopB, sopD and pipD genes were constructed by using latest site-specific group II intron mutagenesis approach to reveal the pathogenicity of the virulence factors. Overall, we observed that the mutations in sopB, sopD and pipD genes of both serovars did not exhibit significant decrease in virulence towards the nematode. This may indicate that these virulence effectors may not be universal virulence factors involved in conserved innate immunity. There are significant phenotypic differences amongst strains carrying sopB, sopD and pipD gene mutations via the analysis of biochemical profiles of the bacteria. Interestingly, mutant strains displayed different susceptibility to chemical stressors from several distinct pharmacological and structural classes when compared to its isogenic parental strains. These metabolic and chemosensitivity assays also revealed multiple roles of Salmonella virulence factors in nutrient metabolism and antibiotic resistance.
    Matched MeSH terms: Caenorhabditis elegans/microbiology; Caenorhabditis elegans/physiology
  3. Wetchakul P, Goon JA, Adekoya AE, Olatunji OJ, Ruangchuay S, Jaisamut P, et al.
    BMC Complement Altern Med, 2019 Aug 13;19(1):209.
    PMID: 31409340 DOI: 10.1186/s12906-019-2626-1
    BACKGROUND: The imbalance between the generation of free radicals and natural cellular antioxidant defenses, known as oxidative stress, can cause oxidation of biomolecules and further contribute to aging-associated diseases. The purpose of this study was to evaluate the antioxidant capacities of Thai traditional tonifying preparation, Jatu-Phala-Tiga (JPT) and its herbal ingredients consisting of Phyllanthus emblica, Terminalia arjuna, Terminalia chebula, and Terminalia bellirica and further assess its effect on longevity.

    METHOD: Antioxidant activities of various extracts obtained from JPT and its herbal components were carried out using well-established methods including metal chelating, free radical scavenging, and ferric reducing antioxidant power assays. Qualitative analysis of the chemical composition from JPT water extract was done by high-performance liquid chromatography tandem with electrospray ionisation mass spectrometry. The effect of JPT water extract on the lifespan of Caenorhabditis elegans were additionally described.

    RESULTS: Among the extracts, JPT water extract exerted remarkable antioxidant activities as compared to the extracts from other solvents and individual constituting plant extract. JPT water extract was found to possess the highest metal chelating activity, with an IC50 value of 1.75 ± 0.05 mg/mL. Moreover, it exhibited remarkable scavenging activities towards DPPH, ABTS, and superoxide anion radicals, with IC50 values of 0.31 ± 0.02, 0.308 ± 0.004, and 0.055 ± 0.002 mg/mL, respectively. The ORAC and FRAP values of JPT water extract were 40.338 ± 2.273 μM of Trolox/μg of extract and 23.07 ± 1.84 mM FeSO4/mg sample, respectively. Several well-known antioxidant-related compounds including amaronols, quinic acid, gallic acid, fertaric acid, kurigalin, amlaic acid, isoterchebin, chebulagic acid, ginkgolide C, chebulinic acid, ellagic acid, and rutin were found in this extract. Treatment with JPT water extract at 1 and 5 mg/mL increased C. elegans lifespan under normal growth condition (7.26 ± 0.65 vs. 10.4 0± 0.75 (p 

    Matched MeSH terms: Caenorhabditis elegans/drug effects*; Caenorhabditis elegans/growth & development*
  4. Kumarasingha R, Young ND, Yeo TC, Lim DSL, Tu CL, Palombo EA, et al.
    Parasit Vectors, 2019 Apr 25;12(1):181.
    PMID: 31023350 DOI: 10.1186/s13071-019-3429-4
    BACKGROUND: Natural compounds from plants are known to provide a source of anthelmintic molecules. In previous studies, we have shown that plant extracts from the plant Picria fel-terrae Lour. and particular fractions thereof have activity against the free-living nematode Caenorhabditis elegans, causing quite pronounced stress responses in this nematode. We have also shown that a fraction, designated Pf-fraction 5, derived from this plant has a substantial adverse effect on this worm; however, nothing is known about the molecular processes affected in the worm. In the present study, we explored this aspect.

    RESULTS: Key biological processes linked to upregulated genes (n = 214) included 'response to endoplasmic reticulum stress' and 'lipid metabolism', and processes representing downregulated genes (n = 357) included 'DNA-conformation change' and 'cellular lipid metabolism'.

    CONCLUSIONS: Exposure of C. elegans to Pf-fraction 5 induces significant changes in the transcriptome. Gene ontology analysis suggests that Pf-fraction 5 induces endoplasmic reticulum and mitochondrial stress, and the changes in gene expression are either a direct or indirect consequence of this. Further work is required to assess specific responses to sub-fractions of Pf-fraction 5 in time-course experiments in C. elegans, to define the chemical(s) with potent anthelmintic properties, to attempt to unravel their mode(s) of action and to assess their selectivity against nematodes.

    Matched MeSH terms: Caenorhabditis elegans
  5. Gagman HA, Him NAIIN, Ahmad H, Sulaiman SF, Zakaria R, Termizi FHM
    Trop Life Sci Res, 2020 Oct;31(3):145-159.
    PMID: 33214861 DOI: 10.21315/tlsr2020.31.3.10
    Gastrointestinal nematode infections can cause great losses in revenue due to decrease livestock production and animal death. The use of anthelmintic to control gastrointestinal nematode put a selection pressure on nematode populations which led to emergence of anthelmintic resistance. Because of that, this study was carried out to investigate the efficacy of aqueous and methanol extract of Cassia siamea against the motility of C. elegans Bristol N2 and C. elegans DA1316. Caenorhabditis elegans Bristol N2 is a susceptible strain and C. elegans DA1316 is an ivermectin resistant strain. In vitro bioassay of various concentrations of (0.2, 0.6, 0.8, 1.0 and 2.0 mg mL-1) aqueous and methanol extracts of C. siamea was conducted against the motility of L4 larvae of C. elegans Bristol N2 and C. elegans DA1316. The L4 larvae were treated with 0.02 μg mL-1 of ivermectin served as positive control while those in M9 solution served as negative control. The activity of the extracts was observed after 24 h and 48 h. A significant difference was recorded in the extract performance compared to control at (P < 0.001) after 48 h against the motility of the larvae of both strains. The methanol extracts inhibited the motility of C. elegans Bristol N2 by 86.7% as well as DA1316 up to 84.9% at 2.0 mg mL-1 after 48 h. The methanol extract was more efficient than aqueous extract (P < 0.05) against the motility of both strains of C. elegans. Cassia siamea may be used as a natural source of lead compounds for the development of alternative anthelmintic against parasitic nematodes as well ivermectin resistant strains of nematodes.
    Matched MeSH terms: Caenorhabditis elegans
  6. Lim MP, Firdaus-Raih M, Nathan S
    Front Microbiol, 2016;7:1436.
    PMID: 27672387 DOI: 10.3389/fmicb.2016.01436
    Burkholderia pseudomallei, the causative agent of melioidosis, is among a growing number of bacterial pathogens that are increasingly antibiotic resistant. Antimicrobial peptides (AMPs) have been investigated as an alternative approach to treat microbial infections, as generally, there is a lower likelihood that a pathogen will develop resistance to AMPs. In this study, 36 candidate Caenorhabditis elegans genes that encode secreted peptides of <150 amino acids and previously shown to be overexpressed during infection by B. pseudomallei were identified from the expression profile of infected nematodes. RNA interference (RNAi)-based knockdown of 12/34 peptide-encoding genes resulted in enhanced nematode susceptibility to B. pseudomallei without affecting worm fitness. A microdilution test demonstrated that two peptides, NLP-31 and Y43C5A.3, exhibited anti-B. pseudomallei activity in a dose dependent manner on different pathogens. Time kill analysis proposed that these peptides were bacteriostatic against B. pseudomallei at concentrations up to 8× MIC90. The SYTOX green assay demonstrated that NLP-31 and Y43C5A.3 did not disrupt the B. pseudomallei membrane. Instead, gel retardation assays revealed that both peptides were able to bind to DNA and interfere with bacterial viability. In parallel, microscopic examination showed induction of cellular filamentation, a hallmark of DNA synthesis inhibition, of NLP-31 and Y43C5A.3 treated cells. In addition, the peptides also regulated the expression of inflammatory cytokines in B. pseudomallei infected macrophage cells. Collectively, these findings demonstrate the potential of NLP-31 and Y43C5A.3 as anti-B. pseudomallei peptides based on their function as immune modulators.
    Matched MeSH terms: Caenorhabditis elegans
  7. Fatin SN, Boon-Khai T, Shu-Chien AC, Khairuddean M, Al-Ashraf Abdullah A
    Front Microbiol, 2017;8:2267.
    PMID: 29201023 DOI: 10.3389/fmicb.2017.02267
    The resistance of Pseudomonas aeruginosa to conventional antimicrobial treatment is a major scourge in healthcare. Therefore, it is crucial that novel potent anti-infectives are discovered. The aim of the present study is to screen marine actinomycetes for chemical entities capable of overcoming P. aeruginosa infection through mechanisms involving anti-virulence or host immunity activities. A total of 18 actinomycetes isolates were sampled from marine sediment of Songsong Island, Kedah, Malaysia. Upon confirming that the methanolic crude extract of these isolates do not display direct bactericidal activities, they were tested for capacity to rescue Caenorhabditis elegans infected with P. aeruginosa strain PA14. A hexane partition of the extract from one isolate, designated as Streptomyces sp. CCB-PSK207, could promote the survival of PA14 infected worms by more than 60%. Partial 16S sequence analysis on this isolate showed identity of 99.79% with Streptomyces sundarbansensis. This partition did not impair feeding behavior of C. elegans worms. Tested on PA14, the partition also did not affect bacterial growth or its ability to colonize host gut. The production of biofilm, protease, and pyocyanin in PA14 were uninterrupted, although there was an increase in elastase production. In lys-7::GFP worms, this partition was shown to induce the expression of lysozyme 7, an important innate immunity defense molecule that was repressed during PA14 infection. GC-MS analysis of the bioactive fraction of Streptomyces sp. CCB-PSK207 revealed the presence of methyl esters of branched saturated fatty acids. In conclusion, this is the first report of a marine actinomycete producing metabolites capable of rescuing C. elegans from PA14 through a lys-7 mediated activity.
    Matched MeSH terms: Caenorhabditis elegans
  8. Kumarasingha R, Palombo EA, Bhave M, Yeo TC, Lim DS, Tu CL, et al.
    Int J Parasitol, 2014 Apr;44(5):291-8.
    PMID: 24583111 DOI: 10.1016/j.ijpara.2014.01.008
    Traditional healers in Sarawak, Malaysia, use plants such as Picria fel-terrae, Linariantha bicolor and Lansium domesticum to treat gastrointestinal infections. This study aimed to test whether their nematocidal activities could be confirmed in vitro using highly standardised Caenorhabditis elegans models. We applied eight different ethanol solubilised plant extracts and two commercial anthelmintic drugs to larval and adult stages of C. elegans in vitro. Seven C. elegans strains were evaluated, one wild type and six strains with GFP-tagged stress response pathways to help characterise and compare the pathways affected by plant extracts. Our in vitro screen confirmed that both of the commercial anthelmintic drugs and five of the eight traditionally used plant extracts had significant nematocidal activity against both larval and adult C. elegans. The most effective extracts were from P. fel-terrae. The plant extracts triggered different stress response pathways from the commercial anthelmintic drugs. This study showed that using traditional knowledge of plant medicinal properties in combination with a C. elegans in vitro screen provided a rapid and economical test with a high hit rate compared with the random screening of plants for nematocidal activities. The use of transgenic C. elegans strains may allow this approach to be refined further to investigate the mode of action of active extracts.
    Matched MeSH terms: Caenorhabditis elegans/drug effects*
  9. Yusop SNW, Imran S, Adenan MI, Sultan S
    Steroids, 2020 12;164:108735.
    PMID: 32976918 DOI: 10.1016/j.steroids.2020.108735
    The fungal transformations of medroxyrogesterone (1) were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus. The metabolites obtained are as following: 6β, 20-dihydroxymedroxyprogesterone (2), 12β-hydroxymedroxyprogesterone (3), 6β, 11β-dihydroxymedroxyprogesterone (4), 16β-hydroxymedroxyprogesterone (5), 11α, 17-dihydroxy-6α-methylpregn-4-ene-3, 20-dione (6), 11-oxo-medroxyprogesterone (7), 6α-methyl-17α-hydroxypregn-1,4-diene-3,20-dione (8), and 6β-hydroxymedroxyprogesterone (9), 15β-hydroxymedroxyprogesterone (10), 6α-methyl-17α, 11β-dihydroxy-5α-pregnan-3, 20-dione (11), 11β-hydroxymedroxyprogesterone (12), and 11α, 20-dihydroxymedroxyprogesterone (13). Among all the microbial transformed products, the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Compounds 12, 5, 6, 9, 11, and 3 (in descending order of activity) also showed some extent of activity against SH-SY5Y tumour cell line. The never been reported biotransformed product, 2, showed the most potent inhibitory activity against acetylcholinesterase. Molecular modelling studies were carried out to understand the observed experimental activities, and also to obtain more information on the binding mode and the interactions between the biotransformed products, and enzyme.
    Matched MeSH terms: Caenorhabditis elegans/metabolism
  10. Ramli NS, Eng Guan C, Nathan S, Vadivelu J
    PLoS One, 2012;7(9):e44104.
    PMID: 22970167 DOI: 10.1371/journal.pone.0044104
    Burkholderia pseudomallei, a Gram-negative saprophytic bacterium, is the causative agent of the potentially fatal melioidosis disease in humans. In this study, environmental parameters including temperature, nutrient content, pH and the presence of glucose were shown to play a role in in vitro biofilm formation by 28 B. pseudomallei clinical isolates, including four isolates with large colony variants (LCVs) and small colony variants (SCVs) morphotypes. Enhanced biofilm formation was observed when the isolates were tested in LB medium, at 30 °C, at pH 7.2, and in the presence of as little as 2 mM glucose respectively. It was also shown that all SVCs displayed significantly greater capacity to form biofilms than the corresponding LCVs when cultured in LB at 37 °C. In addition, octanoyl-homoserine lactone (C(8)-HSL), a quorum sensing molecule, was identified by mass spectrometry analysis in bacterial isolates referred to as LCV CTH, LCV VIT, SCV TOM, SCV CTH, 1 and 3, and the presence of other AHL's with higher masses; decanoyl-homoserine lactone (C(10)-HSL) and dodecanoyl-homoserine lactone (C(12)-HSL) were also found in all tested strain in this study. Last but not least, we had successfully acquired two Bacillus sp. soil isolates, termed KW and SA respectively, which possessed strong AHLs degradation activity. Biofilm formation of B. pseudomallei isolates was significantly decreased after treated with culture supernatants of KW and SA strains, demonstrating that AHLs may play a role in B. pseudomallei biofilm formation.
    Matched MeSH terms: Caenorhabditis elegans/cytology; Caenorhabditis elegans/drug effects
  11. Yuen CW, Murugaiyah V, Najimudin N, Azzam G
    J Ethnopharmacol, 2021 Feb 10;266:113418.
    PMID: 32991971 DOI: 10.1016/j.jep.2020.113418
    ETHNOPHARMACOLOGICAL RELEVANCE: Danshen, is a traditional Chinese medicine obtained from the dried root and rhizome of Salvia miltiorrhiza Bunge. It is known to be used for neurological disorder including for Alzheimer's disease (AD). This study uncovers the effect of Danshen water extract on the Alzheimer's disease model of C.elegans.

    MATERIAL AND METHODS: The composition of Danshen water extract was determined using (High Performance Liquid Chromatography (HPLC). Then Thioflavin T assay was used to determined if Danshen water extract could prevent the aggregation of amyloid-β peptide (Aβ). Alzheimer's disease C.elegans model was used to determine the effect of Danshen water extract. Finally, the reactive oxygen species (ROS) was determined using the 2,7-dichlorofuorescein diacetate method.

    RESULTS: In this study, we found that standardized Danshen water extract that contains danshensu (1.26%), salvianolic acid A (0.35%) and salvianolic acid B (2.21%) are able to bind directly to Aβ and prevents it from aggregating. The IC50 for the inhibition of Aβ aggregation by Danshen water extract was 0.5 mg/ml. In the AD model of C.elegans, Danshen water extract managed to alleviates the paralysis phenotype. Furthermore, the administration of Danshen water extract displayed antioxidant properties toward the Aβ-induced oxidative stress.

    CONCLUSIONS: AD is a widespread neurodegenerative disease attributed to the accumulation of extracellular plaques comprising Aβ. Danshen water extract could significantly reduce the progress of paralysis in the AD model of C. elegans, showing promising results with its antioxidant properties. It can be concluded that Danshen water extract could potentially serve as a therapeutic for AD.

    Matched MeSH terms: Caenorhabditis elegans/drug effects
  12. Ali NH, Amin MCIM, Ng SF
    J Biomater Sci Polym Ed, 2019 06;30(8):629-645.
    PMID: 30896336 DOI: 10.1080/09205063.2019.1595892
    Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing wounds. It was found that the increased resistance of biofilms to antibiotics allows wound infections to persist chronically in spite of antibiotic therapy. In this study, the reduced form of graphene oxide (rGO) was explored as plausible antibiofilm agents. The rGO was synthesized via reducing the functional groups of GO. Then, rGO were characterized using zetasizer, X-ray photoelectron spectroscopy, UV-Vis spectroscopy and FESEM. The rGO were then formulated into sodium carboxymethyl cellulose (NaCMC) hydrogels to form rGO hydrogel and tested for antibiofilm activities in vitro using XTT test, and in vivo biofilm formation assay using nematodes C. elegans. Reduced GO hydrogel was successfully formed by reducing the functional groups of GO, and a reduction of up to 95% of functional groups was confirmed with X-ray photoelectron spectroscopy analysis. XTT tests confirmed that rGO hydrogels reduced biofilm formation by S. aureus (81-84%) and P. aeruginosa (50-62%). Fluorescence intensity also confirmed that rGO hydrogel can inhibit biofilm bacteria in C. elegans experiments. This study implied that rGO hydrogel is an effective antibiofilm agent for infected wounds.
    Matched MeSH terms: Caenorhabditis elegans/drug effects
  13. Zaman K, Rahim F, Taha M, Sajid M, Hayat S, Nawaz M, et al.
    Bioorg Chem, 2021 10;115:105199.
    PMID: 34329995 DOI: 10.1016/j.bioorg.2021.105199
    Synthesis of quinoline analogs and their urease inhibitory activities with reference to the standard drug, thiourea (IC50 = 21.86 ± 0.40 µM) are presented in this study. The inhibitory activity range is (IC50 = 0.60 ± 0.01 to 24.10 ± 0.70 µM) which displayed that it is most potent class of urease inhibitor. Analog 1-9, and 11-13 emerged with many times greater antiurease potential than thiourea, in which analog 1, 2, 3, 4, 8, 9, and 11 (IC50 = 3.50 ± 0.10, 7.20 ± 0.20, 1.30 ± 0.10, 2.30 ± 0.10, 0.60 ± 0.01, 1.05 ± 0.10 and 2.60 ± 0.10 µM respectively) were appeared the most potent ones among the series. In this context, most potent analogs such as 1, 3, 4, 8, and 9 were further subjected for their in vitro antinematodal study against C. elegans to examine its cytotoxicity under positive control of standard drug, Levamisole. Consequently, the cytotoxicity profile displayed that analogs 3, 8, and 9 were found with minimum cytotoxic outline at higher concentration (500 µg/mL). All analogs were characterized through 1H NMR, 13C NMR and HR-EIMS. The protein-ligand binding interaction for most potent analogs was confirmed via molecular docking study.
    Matched MeSH terms: Caenorhabditis elegans/drug effects*
  14. Eng SA, Nathan S
    Front Microbiol, 2015;6:290.
    PMID: 25914690 DOI: 10.3389/fmicb.2015.00290
    The tropical pathogen Burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. However, the development of antibiotic resistance is emerging as a threat to this form of treatment. To meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. We suggest that the use of molecules or compounds that are non-bactericidal (bacteriostatic) will reduce or abolish the development of resistance by the pathogen. In this study, we adopted the established Caenorhabditis elegans-B. pseudomallei infection model to screen a collection of natural products for any that are able to extend the survival of B. pseudomallei infected worms. Of the 42 natural products screened, only curcumin significantly improved worm survival following infection whilst not affecting bacterial growth. This suggested that curcumin promoted B. pseudomallei-infected worm survival independent of pathogen killing. To validate that the protective effect of curcumin was directed toward the pathogen, bacteria were treated with curcumin prior to infection. Worms fed with curcumin-treated bacteria survived with a significantly extended mean-time-to-death (p < 0.0001) compared to the untreated control. In in vitro assays, curcumin reduced the activity of known virulence factors (lipase and protease) and biofilm formation. To determine if other bacterial genes were also regulated in the presence of curcumin, a genome-wide transcriptome analysis was performed on curcumin-treated pathogen. A number of genes involved in iron acquisition and transport as well as genes encoding hypothetical proteins were induced in the presence of curcumin. Thus, we propose that curcumin may attenuate B. pseudomallei by modulating the expression of a number of bacterial proteins including lipase and protease as well as biofilm formation whilst concomitantly regulating iron transport and other proteins of unknown function.
    Matched MeSH terms: Caenorhabditis elegans
  15. Wong YC, Abd El Ghany M, Ghazzali RNM, Yap SJ, Hoh CC, Pain A, et al.
    Front Microbiol, 2018;9:1118.
    PMID: 29896180 DOI: 10.3389/fmicb.2018.01118
    A Burkholderia cenocepacia infection usually leads to reduced survival and fatal cepacia syndrome in cystic fibrosis patients. The identification of B. cenocepacia essential genes for in vivo survival is key to designing new anti-infectives therapies. We used the Transposon-Directed Insertion Sequencing (TraDIS) approach to identify genes required for B. cenocepacia survival in the model infection host, Caenorhabditis elegans. A B. cenocepacia J2315 transposon pool of ∼500,000 mutants was used to infect C. elegans. We identified 178 genes as crucial for B. cenocepacia survival in the infected nematode. The majority of these genes code for proteins of unknown function, many of which are encoded by the genomic island BcenGI13, while other gene products are involved in nutrient acquisition, general stress responses and LPS O-antigen biosynthesis. Deletion of the glycosyltransferase gene wbxB and a histone-like nucleoid structuring (H-NS) protein-encoding gene (BCAL0154) reduced bacterial accumulation and attenuated virulence in C. elegans. Further analysis using quantitative RT-PCR indicated that BCAL0154 modulates B. cenocepacia pathogenesis via transcriptional regulation of motility-associated genes including fliC, fliG, flhD, and cheB1. This screen has successfully identified genes required for B. cenocepacia survival within the host-associated environment, many of which are potential targets for developing new antimicrobials.
    Matched MeSH terms: Caenorhabditis elegans
  16. Mat Jalaluddin NS, Othman RY, Harikrishna JA
    Crit Rev Biotechnol, 2018 Sep 09.
    PMID: 30198341 DOI: 10.1080/07388551.2018.1496064
    It has only been about 20 years since the first Nobel Prize-winning work on RNA interference (RNAi) in Caenorhabditis elegans was published in the journal Nature. Fast forward to today, and the use of RNA molecules as gene-silencing elements in crops has helped scientists to unveil possible solutions to the global problems of agricultural losses due to pests, viruses, pathogens, and to other abiotic and biotic stresses. The recent proliferation of publications suggests that the technology has gained significant attention and received ample funding support. In this article, an attempt has been made to visualize recent trends in Research & Development (R&D) investment in this field by analyzing top cited scholarly articles, patent trends, and commercialization activity. The publication and citation analysis identified that the development of RNAi-based crops conferring resistance against viruses, fungi, and pests are at the forefront of RNAi research and that Chinese and US institutions are the leaders in this field. The patent landscape analysis for RNAi technology over all aspects related to RNAi-derived crops provides an overview of patenting activity from a geographical, organizational, and legal perspective. Such an exercise is pivotal to industry players and public institutions aiming at creating intellectual property that is commercially appealing. An upswing in commercial interests in this technology in recent years is reflected by a consistent number of patent filings in US, European, and Chinese patent offices, with multinational giant firms as the most prolific patent filers. The expanding RNAi commercialization landscape is supported by a series of strategic partnerships, licensing agreements, and acquisitions created between agribusinesses, public research institutions, and startup companies. From key observations, we would like to highlight that such investments have very positive impacts on the development of RNAi technology. Nonetheless, the success of this technology is dependent on several factors, such as financial requirements, the complexity, and timeframe of the entire development process, as well as stringent regulations imposed by the relevant authorities. In most countries, RNAi-based transgenic crops are still considered as a genetically modified (GM) product, which necessitates the crops to undergo rigorous evaluation before approval is granted. Recent advancements in exogenous RNAi-derived biopesticides have provided a nontransgenic alternative to GM crops. However, challenges still remain in the form of technical hurdles and regulatory ambiguities surrounding this emerging technology. Its full potential remains to be realized.
    Matched MeSH terms: Caenorhabditis elegans
  17. Kong C, Chee CF, Richter K, Thomas N, Abd Rahman N, Nathan S
    Sci Rep, 2018 02 09;8(1):2758.
    PMID: 29426873 DOI: 10.1038/s41598-018-21141-2
    Staphylococcus aureus is a major cause of nosocomial infections and secretes a diverse spectrum of virulence determinants as well as forms biofilm. The emergence of antibiotic-resistant S. aureus highlights the need for alternative forms of therapeutics other than conventional antibiotics. One route to meet this need is screening small molecule derivatives for potential anti-infective activity. Using a previously optimized C. elegans - S. aureus small molecule screen, we identified a benzimidazole derivative, UM-C162, which rescued nematodes from a S. aureus infection. UM-C162 prevented the formation of biofilm in a dose-dependent manner without interfering with bacterial viability. To examine the effect of UM-C162 on the expression of S. aureus virulence genes, a genome-wide transcriptome analysis was performed on UM-C162-treated pathogen. Our data indicated that the genes associated with biofilm formation, particularly those involved in bacterial attachment, were suppressed in UM-C162-treated bacteria. Additionally, a set of genes encoding vital S. aureus virulence factors were also down-regulated in the presence of UM-C162. Further biochemical analysis validated that UM-C162-mediated disruption of S. aureus hemolysins, proteases and clumping factors production. Collectively, our findings propose that UM-C162 is a promising compound that can be further developed as an anti-virulence agent to control S. aureus infections.
    Matched MeSH terms: Caenorhabditis elegans
  18. Zulazmi NA, Arulsamy A, Ali I, Zainal Abidin SA, Othman I, Shaikh MF
    CNS Neurosci Ther, 2021 Apr;27(4):381-402.
    PMID: 33539662 DOI: 10.1111/cns.13590
    Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non-human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non-mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non-mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non-mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non-mammalian TBI models have advantages over mammalian models especially for rapid, cost-effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research.
    Matched MeSH terms: Caenorhabditis elegans
  19. Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S
    PMID: 24393217 DOI: 10.1186/1472-6882-14-4
    The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.
    Matched MeSH terms: Caenorhabditis elegans/microbiology*
  20. Roslan R, Othman RM, Shah ZA, Kasim S, Asmuni H, Taliba J, et al.
    Comput Biol Med, 2010 Jun;40(6):555-64.
    PMID: 20417930 DOI: 10.1016/j.compbiomed.2010.03.009
    Protein-protein interactions (PPIs) play a significant role in many crucial cellular operations such as metabolism, signaling and regulations. The computational methods for predicting PPIs have shown tremendous growth in recent years, but problem such as huge false positive rates has contributed to the lack of solid PPI information. We aimed at enhancing the overlap between computational predictions and experimental results in an effort to partially remove PPIs falsely predicted. The use of protein function predictor named PFP() that are based on shared interacting domain patterns is introduced in this study with the purpose of aiding the Gene Ontology Annotations (GOA). We used GOA and PFP() as agents in a filtering process to reduce false positive pairs in the computationally predicted PPI datasets. The functions predicted by PFP() were extracted from cross-species PPI data in order to assign novel functional annotations for the uncharacterized proteins and also as additional functions for those that are already characterized by the GO (Gene Ontology). The implementation of PFP() managed to increase the chances of finding matching function annotation for the first rule in the filtration process as much as 20%. To assess the capability of the proposed framework in filtering false PPIs, we applied it on the available S. cerevisiae PPIs and measured the performance in two aspects, the improvement made indicated as Signal-to-Noise Ratio (SNR) and the strength of improvement, respectively. The proposed filtering framework significantly achieved better performance than without it in both metrics.
    Matched MeSH terms: Caenorhabditis elegans Proteins
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