Candida albicans has been reported globally as the most widespread pathogenic species contributing candidiasis from superficial to systemic infections in immunocompromised individuals. Their metabolic adaptation depends on glyoxylate cycle to survive in nutrientlimited host. The long term usage of fungistatic drugs and the lack of cidal drugs frequently result in strains that could resist commonly used antifungals and display multidrug resistance (MDR). In search of potential therapeutic intervention and novel fungicidals, we have explored a plant alkaloids, namely arborinine and graveoline for its antifungal potential. Alkaloids belongs to Rutaceae family have been reported with numerous antimicrobial activities. In this study, we aimed to isolate and identify the antifungal active alkaloids of R. angustifolia and assess antifungal effect targeting C. albicans isocitrate lyase (ICL) gene which regulates isocitrate lyase, key enzyme in glyoxylate cycle contributing to the virulence potential of C. albicans. Alkaloids were extracted by bioassay guided isolation technique which further identified by TLC profile and compared with the standard through HPLC and NMR analysis. The antifungal activities of the extracted alkaloids were quantified by means of MIC (Minimum Inhibitory Concentration). The gene expression of the targeted gene upon treatment was analysed using RT-qPCR and western blot. Additionally, this study looked at the drug-likeness and potential toxicity effect of the active alkaloid compounds in silico analysis. Spectroscopic analysis showed that the isolated active alkaloids were characterized as acridone, furoquinoline, 4-quinolone known as arborinine and graveoline. Results showed that each compound significantly inhibited the growth of C. albicans at the dose of 250 to 500 µg/mL which confirm its antifungal activity. Each alkaloid was found to successfully downregulate the expression of both ICL1 gene CaIcl1 protein. Finally, ADMET analysis suggests a good prediction of chemical properties, namely absorption, distribution, metabolism, excretion and toxicity (ADMET) that will contribute in drug discovery and development later on.
Candida albicans is a commensal yeast commonly found on the skin and in the body. However, in immunocompromised individuals, the fungi could cause local and systemic infections. The carbon source available plays an important role in the establishment of C. albicans infections. The fungi's ability to assimilate a variety of carbon sources plays a vital role in its colonization, and by extension, its fitness and pathogenicity, as it often inhabits niches that are glucose-limited but rich in alternative carbon sources. A difference in carbon sources affect the growth and mating of C. albicans, which contributes to its pathogenicity as proliferation helps the fungi colonize its environment. The carbon source also affects its metabolism and signaling pathways, which are integral parts of the fungi's fitness and pathogenicity. As a big percentage of the carbon assimilated by C. albicans goes to cell wall biogenesis, the availability of different carbon sources will result in cell walls with variations in rigidity, adhesion, and surface hydrophobicity. In addition to the biofilm formation of the fungi, the carbon source also influences whether the fungi grow in yeast- or mycelial-form. Both forms play different roles in C. albicans’s infection process. A better understanding of the role of the carbon sources in C. albicans’s pathogenicity would contribute to more effective treatment solutions for fungal infections.
Background: Candida glabrata is a ubiquitous organism and this species is one of the normal floras that commonly found in oral cavity, gastrointestinal and vaginal tract. However, they can be pathogenic and caused serious infection that more likely to occur in immunocompromised patients. Widespread and increased usage of immunosuppressive therapies with the additional of broad-spectrum antibiotic treatment can also lead to the significant increment of Candida infections. Candida species can cause nosocomial infection that associated with alarming high mortality rate worldwide. C. glabrata is one of the Candida species that raise an attention of a researcher due to their high resistance to certain drugs and antifungal as well as host immune system.Objective: To investigate certain aspects of the C. glabrata that contributes to their resistance to drugs and as host in immune system.Results: Microorganisms including Candida have an ability to evolve in order to sustain their survival and it is creating a new microbial community that are more resistant. C. glabrata possessed several strategies for their resistance including production of biofilm, genomic plasticity as well as chromatin alteration. On the other hand, their resistance may cause by the mutation in certain gene. Besides, they also use a variety of mechanisms that enable their adaptation works successfully and their survival as host in immune system. Conclusion:A significant number of researches have been conducted to elucidate resistant mechanism of C. glabrata thus, much information has been gained on how their resistant mechanism works and has enhanced our knowledge on the virulence and resistance mechanisms associated with Candida species especially C. glabrata. Further studies and investigation in this area are crucial particularly on the identification and development of new targets for novel therapeutics against these recently emerged pathogens.
ABSTRAKSampi atau mantera merupakan puisi tradisional kaum Iban dalam kategori invokasi yang berfungsi sebagai permohonan doa untuk mendapatkan pertolongan atau perlindungan. Kata-kata dalam sampi yang dilafazkan kepada Petara (Dewa-dewi) digayakan dengan bahasa kiasan metafora menambahkan lagi keindahan seni berpuisi dikalangan masyarakat Iban. Kajian ini bertujuan untuk menganalisis unsur-unsur yang membentuk bahasa kiasan metafora dalam mantera perhumaan (sampi umai) masyarakat Iban. Berasaskan pendekatan secara kualitatif, kaedah deskriptif digunakan untuk mengkaji dua buah sampi perhumaan yang diambil daripada buku Sampi Enggau Biau. Analisis kandungan digunakan untuk menganalisis bahasa kiasan yang terdapat dalam sampi. Dapatan kajian menunjukkan bahasa kiasan sampi terdiri daripada unsur alam seperti tumbuhan, haiwan, dan manusia, yang disesuaikan dengan unsur bukan alam yang dicipta dan menjadi budaya dalam kehidupan mereka. Unsur-unsur ini digunakan untuk menyatakan warisan tradisi, merendahkan diri, persembahan sajian (piring), kehebatan perwira, kecantikan wanita dan hasil padi. Implikasi kajian ini menunjukkan penggunaan unsur alam dan bukan alam dalam bahasa kiasan metafora menambahkan pengetahuan pengamal tentang kemahiran berbahasa. Kata kunci Bahasa kiasan; metafora; sampi perhumaan; alam; bukan alam ABSTRACT Sampi or mantra is a traditional poem of Iban in the category of invocation which functioned as a prayer request for help or protection. The words which uttered in sampi to Petara (Goddess) styled with the figurative language of metaphor enhances the beauty of poetry among the Iban community. This study aims to analyse the elements that formed the figurative languages of metaphor in the paddy cultivation prayers (sampi umai). Based on qualitative approach, descriptive method was used to examine two paddy cultivation prayers which were taken from a book entitled SampiEnggauBiau. Content analysis was used to analyse the figurative language in the sampi. Results showed the figurative language of metaphor in the Iban sampi consist of nature such as plants, animals and human which are then adjusted to the non-nature elements which were made and became a culture in their lives. These elements were used to symbolise the inheritance of tradition, humbleness, offering presentation (piring), the greatness of the warrior, the beauty of woman, crowds and the harvest of paddy. The implications of this study show that the use of nature and non-nature elements in the metaphor enhances practitioner's knowledge about the language.
This topic was to examine the impact of galactose or fructose upon the assimilation of secondary carbon sources by Candida albicans. C. albicans ICL1 gene is repressed upon addition of 2% galactose or fructose to lactate-and oleic acid-grown cells. Further studies on CaFOX2, CaFBP1 and CaMLS1 transcripts in response to galactose or fructose on assimilation of lactate and oleic acid resulted in repression of these genes. The CaICL1 gene, which encode the glyoxylate cycles enzymes isocitrate lyase are required for growth on non-fermentable carbon sources. However, the enzyme CaIcl1 was not destabilized by galactose, but was degraded in response to fructose. In contrast, S. cerevisiae Icl1 has retained the molecular apparatus of protein degradation in response to either galactose or fructose. Screening of ubiquitination site by http://www.ubpred.org/ showed that C. albicans lacks ubiquitination site in gluconeogenic and glyoxylate cycles enzymes as compare to S. cerevisiae. Addition of a putative S. cerevisiae ubiquitination site carboxy terminus of CaIcl1 led to galactose-accelerated degradation of this protein in C. albicans cell via a ubiquitin-dependent process. In the other hand, CaIcl prior to addition of ubiquitination site was degraded upon exposure to fructose; addition of S. cerevisiae ubiquitination site to CaIcl1 further increased the speed of protein degradation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.