Displaying publications 1 - 20 of 21 in total

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  1. Fulltext The glyoxylate cycle and alternative carbon metabolism as metabolic adaptation strategies of Candida glabrata: perspectives from Candida albicans and Saccharomyces cerevisiae
    Chew SY, Chee WJY, Than LTL
    J Biomed Sci, 2019 Jul 13;26(1):52.
    PMID: 31301737 DOI: 10.1186/s12929-019-0546-5
    BACKGROUND: Carbon utilization and metabolism are fundamental to every living organism for cellular growth. For intracellular human fungal pathogens such as Candida glabrata, an effective metabolic adaptation strategy is often required for survival and pathogenesis. As one of the host defence strategies to combat invading pathogens, phagocytes such as macrophages constantly impose restrictions on pathogens' access to their preferred carbon source, glucose. Surprisingly, it has been reported that engulfed C. glabrata are able to survive in this harsh microenvironment, further suggesting alternative carbon metabolism as a potential strategy for this opportunistic fungal pathogen to persist in the host.

    MAIN TEXT: In this review, we discuss alternative carbon metabolism as a metabolic adaptation strategy for the pathogenesis of C. glabrata. As the glyoxylate cycle is an important pathway in the utilization of alternative carbon sources, we also highlight the key metabolic enzymes in the glyoxylate cycle and its necessity for the pathogenesis of C. glabrata. Finally, we explore the transcriptional regulatory network of the glyoxylate cycle.

    CONCLUSION: Considering evidence from Candida albicans and Saccharomyces cerevisiae, this review summarizes the current knowledge of the glyoxylate cycle as an alternative carbon metabolic pathway of C. glabrata.

    Matched MeSH terms: Candida glabrata/metabolism*; Candida glabrata/pathogenicity*
  2. In vitro modulation of probiotic bacteria on the biofilm of Candida glabrata
    Chew SY, Cheah YK, Seow HF, Sandai D, Than LT
    Anaerobe, 2015 Aug;34:132-8.
    PMID: 26028405 DOI: 10.1016/j.anaerobe.2015.05.009
    A conspicuous new concept of pathogens living as the microbial societies in the human host rather than free planktonic cells has raised considerable concerns among scientists and clinicians. Fungal biofilms are communities of cells that possess distinct characteristic such as increased resistance to the immune defence and antimycotic agents in comparison to their planktonic cells counterpart. Therefore, inhibition of the biofilm may represent a new paradigm for antifungal development. In this study, we aim to evaluate the in vitro modulation of vulvovaginal candidiasis (VVC)-causing Candida glabrata biofilms using probiotic lactobacilli strains. Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 were shown to have completely inhibited C. glabrata biofilms and the results were corroborated by scanning electron microscopy (SEM), which revealed scanty structures of the mixed biofilms of C. glabrata and probiotic lactobacilli strains. In addition, biofilm-related C. glabrata genes EPA6 and YAK1 were downregulated in response to the probiotic lactobacilli challenges. The present study suggested that probiotic L. rhamnosus GR-1 and L. reuteri RC-14 strains inhibited C. glabrata biofilm by partially impeding the adherence of yeast cells and the effect might be contributed by the secretory compounds produced by these probiotic lactobacilli strains. Further investigations are required to examine and identify the biofilm inhibitory compounds and the mechanism of probiotic actions of these lactobacilli strains.
    Matched MeSH terms: Candida glabrata/genetics; Candida glabrata/growth & development; Candida glabrata/physiology*
  3. Fulltext Transcriptomic and proteomic profiling revealed reprogramming of carbon metabolism in acetate-grown human pathogen Candida glabrata
    Chew SY, Brown AJP, Lau BYC, Cheah YK, Ho KL, Sandai D, et al.
    J Biomed Sci, 2021 Jan 02;28(1):1.
    PMID: 33388061 DOI: 10.1186/s12929-020-00700-8
    BACKGROUND: Emergence of Candida glabrata, which causes potential life-threatening invasive candidiasis, has been widely associated with high morbidity and mortality. In order to cause disease in vivo, a robust and highly efficient metabolic adaptation is crucial for the survival of this fungal pathogen in human host. In fact, reprogramming of the carbon metabolism is believed to be indispensable for phagocytosed C. glabrata within glucose deprivation condition during infection.

    METHODS: In this study, the metabolic responses of C. glabrata under acetate growth condition was explored using high-throughput transcriptomic and proteomic approaches.

    RESULTS: Collectively, a total of 1482 transcripts (26.96%) and 242 proteins (24.69%) were significantly up- or down-regulated. Both transcriptome and proteome data revealed that the regulation of alternative carbon metabolism in C. glabrata resembled other fungal pathogens such as Candida albicans and Cryptococcus neoformans, with up-regulation of many proteins and transcripts from the glyoxylate cycle and gluconeogenesis, namely isocitrate lyase (ICL1), malate synthase (MLS1), phosphoenolpyruvate carboxykinase (PCK1) and fructose 1,6-biphosphatase (FBP1). In the absence of glucose, C. glabrata shifted its metabolism from glucose catabolism to anabolism of glucose intermediates from the available carbon source. This observation essentially suggests that the glyoxylate cycle and gluconeogenesis are potentially critical for the survival of phagocytosed C. glabrata within the glucose-deficient macrophages.

    CONCLUSION: Here, we presented the first global metabolic responses of C. glabrata to alternative carbon source using transcriptomic and proteomic approaches. These findings implicated that reprogramming of the alternative carbon metabolism during glucose deprivation could enhance the survival and persistence of C. glabrata within the host.

    Matched MeSH terms: Candida glabrata/metabolism*
  4. Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations
    Ng TS, Desa MNM, Sandai D, Chong PP, Than LTL
    Infect Genet Evol, 2016 06;40:331-338.
    PMID: 26358577 DOI: 10.1016/j.meegid.2015.09.004
    Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment.
    Matched MeSH terms: Candida glabrata/drug effects*; Candida glabrata/isolation & purification; Candida glabrata/physiology*
  5. Fulltext Physiologically Relevant Alternative Carbon Sources Modulate Biofilm Formation, Cell Wall Architecture, and the Stress and Antifungal Resistance of Candida glabrata
    Chew SY, Ho KL, Cheah YK, Sandai D, Brown AJP, Than LTL
    Int J Mol Sci, 2019 Jun 28;20(13).
    PMID: 31261727 DOI: 10.3390/ijms20133172
    Flexibility in carbon metabolism is pivotal for the survival and propagation of many human fungal pathogens within host niches. Indeed, flexible carbon assimilation enhances pathogenicity and affects the immunogenicity of Candida albicans. Over the last decade, Candida glabrata has emerged as one of the most common and problematic causes of invasive candidiasis. Despite this, the links between carbon metabolism, fitness, and pathogenicity in C. glabrata are largely unexplored. Therefore, this study has investigated the impact of alternative carbon metabolism on the fitness and pathogenic attributes of C. glabrata. We confirm our previous observation that growth on carbon sources other than glucose, namely acetate, lactate, ethanol, or oleate, attenuates both the planktonic and biofilm growth of C. glabrata, but that biofilms are not significantly affected by growth on glycerol. We extend this by showing that C. glabrata cells grown on these alternative carbon sources undergo cell wall remodeling, which reduces the thickness of their β-glucan and chitin inner layer while increasing their outer mannan layer. Furthermore, alternative carbon sources modulated the oxidative stress resistance of C. glabrata as well as the resistance of C. glabrata to an antifungal drug. In short, key fitness and pathogenic attributes of C. glabrata are shown to be dependent on carbon source. This reaffirms the perspective that the nature of the carbon sources available within specific host niches is crucial for C. glabrata pathogenicity during infection.
    Matched MeSH terms: Candida glabrata/drug effects; Candida glabrata/metabolism*; Candida glabrata/physiology
  6. Fulltext Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata
    Chew SY, Ho KL, Cheah YK, Ng TS, Sandai D, Brown AJP, et al.
    Sci Rep, 2019 02 26;9(1):2843.
    PMID: 30808979 DOI: 10.1038/s41598-019-39117-1
    The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.
    Matched MeSH terms: Candida glabrata/enzymology*; Candida glabrata/metabolism; Candida glabrata/pathogenicity
  7. Fulltext Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 exhibit strong antifungal effects against vulvovaginal candidiasis-causing Candida glabrata isolates
    Chew SY, Cheah YK, Seow HF, Sandai D, Than LT
    J Appl Microbiol, 2015 May;118(5):1180-90.
    PMID: 25688886 DOI: 10.1111/jam.12772
    This study investigates the antagonistic effects of the probiotic strains Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 against vulvovaginal candidiasis (VVC)-causing Candida glabrata.
    Matched MeSH terms: Candida glabrata/drug effects; Candida glabrata/growth & development*
  8. Fulltext Short technical communication yeast identification from domestic ragi for food fermentation by PCR method
    Siti Hajar, M.D., Noorhisham, T.K., Nurina, A.
    International Food Research Journal, 2012;19(2):775-777.
    MyJurnal
    In this study polymerase chain reaction (PCR) was used to identify yeast in domestic ragi obtained
    from two local markets in Sarawak and Pahang. These ragi are normally used as a dry starter in food fermentation (tapai) for Pahang (ST2) and Sarawak (ST3) and tuak (ST1) which is an alcoholic drink in Sarawak. Universal primer, NL1 and NL4 were used as a primer in this study to amplify D1/D2 fragment. Based on the result from the sequencing and after the BLAST search of the nucleotide sequences, the strain was confirmed as Candida glabrata (FN424108.) partial 26S rRNA gene, strain IMUFRJ 51955 for ST1, Saccharomyces cerevisiae(EU285514.1) isolate 35 26S ribosomal RNA gene, partial sequence for ST2 sample and Candida glabrata (FN393990.1) partial 26S rRNA gene, strain MUCL 51244 for ST3. All these strains were found in domestic ragi used for food fermentation.
    Matched MeSH terms: Candida glabrata
  9. Fulltext Growth inhibitory response and ultrastructural modification of oral-associated candidal reference strains (ATCC) by Piper betle L. extract
    Nordin MA, Wan Harun WH, Abdul Razak F, Musa MY
    Int J Oral Sci, 2014 Mar;6(1):15-21.
    PMID: 24406634 DOI: 10.1038/ijos.2013.97
    Candida species have been associated with the emergence of strains resistant to selected antifungal agents. Plant products have been used traditionally as alternative medicine to ease mucosal fungal infections. This study aimed to investigate the effects of Piper betle extract on the growth profile and the ultrastructure of commonly isolated oral candidal cells. The major component of P. betle was identified using liquid chromatography-mass spectrophotometry (LC-MS/MS). Seven ATCC control strains of Candida species were cultured in yeast peptone dextrose broth under four different growth environments: (i) in the absence of P. betle extract; and in the presence of P. betle extract at respective concentrations of (ii) 1 mg⋅mL(-1); (iii) 3 mg⋅mL(-1); and (iv) 6 mg⋅mL(-1). The growth inhibitory responses of the candidal cells were determined based on changes in the specific growth rates (µ). Scanning electron microscopy (SEM) was used to observe any ultrastructural alterations in the candida colonies. LC-MS/MS was performed to validate the presence of bioactive compounds in the extract. Following treatment, it was observed that the µ-values of the treated cells were significantly different than those of the untreated cells (P<0.05), indicating the fungistatic properties of the P. betle extract. The candidal population was also reduced from an average of 13.44×10(6) to 1.78×10(6) viable cell counts (CFU)⋅mL(-1). SEM examination exhibited physical damage and considerable morphological alterations of the treated cells. The compound profile from LC-MS/MS indicated the presence of hydroxybenzoic acid, chavibetol and hydroxychavicol in P. betle extract. The effects of P. betle on candida cells could potentiate its antifungal activity.
    Matched MeSH terms: Candida glabrata/drug effects; Candida glabrata/growth & development; Candida glabrata/ultrastructure
  10. Fulltext Suppression of non-Albicans candida species (NAC) biofilm formation by probiotic Streptococcus salivarius
    Sharmeen Nellisa Soffian, Nurul Alia Risma Rismayuddin, Munirah Mokhtar, Mohd Hafiz Arzmi
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):41-41.
    MyJurnal
    Introduction:Candida spp. are most common opportunistic pathogenic yeast that inhabit human oral cavity, epider-mis, gastrointestinal tract, and vagina leading to candidiasis. The transition of this yeast from commensal to potent pathogen is facilitated by numbers of virulence factors including biofilm formation. While most reports on candidi-asis are associated with formation Candida albicans biofilms, however, non-albicans Candida species prevalence is of growing concern. Recently, the use of probiotics as antifungal and antibiofilm has gained an increasing attention. As such, we aim to evaluate the inhibitory effect of monomicrobial and polymicrobial of Streptococcus salivariuson six strains of NAC namely Candida dubliniensis, Candida glabrata, Candida krusei, Candida lusitanaei, Candida parapsilosis and Candida tropicalis. Methods: Antifungal activity of S. salivarius on NAC species was performed using well diffusion method on Mueller Hinton Agar (MHA) and the diameter of inhibition zone were assessed. For formation of monomicrobial biofilm, standardized cell suspensions of NAC species (1 x 105 cells/ml) and probiotic Streptococcus salivarius (1 x 106 cells/ml) were grown in RPMI or nutrient broth media at 37°C for 72 h. Meanwhile to study polymicrobial biofilm of both NAC and S. salivarius, similar protocol was employed by inoculating both microorganisms with a similar cell density as in monomicrobial. Finally, biofilm formation was assessed through quantification of total biomass by crystal violet (CV) assay and the absorbance of adherent biofilm was measured in triplicate at 620nm. Results: Antifungal susceptibility testing of S. salivarius on all six NAC species discerned no zone of inhibition. Furthermore, our results showed variability of monomicrobial and polymicrobial biofilm biomass between NAC species and growth medium. All six polymicrobial NB-grown and RPMI-grown exhibited decreased of the biofilm formation. C. parapsilosis co-cultured with S. salivarius in NB medium had shown lowest biofilm bio-mass by 75.51+_1.34% while in RPMI medium, C. lusitanaei demonstrated with most reduced biofilm biomass by 67.03+_5.19. Conclusion: Our study elucidated the antagonistic relationship between Streptococcus salivarius and non-albicans Candida by supressing the growth of polymicrobial biofilm and pseudohyphae/hyphae of NAC species.
    Matched MeSH terms: Candida glabrata
  11. Fulltext In-vitro antidermatophytic activity of methanolic fractions from entada spiralis ridl. Stem bark and its bioautographic profile
    Aiza Harun, Siti Zaiton Mat So’ad, Norazian Mohd Hassan, Neni Kartini Che Mohd Ramli
    Pertanika Journal of Science & Technology, 2014;22(1):113-121.
    MyJurnal
    This study was performed to evaluate the antifungal activities of methanolic fractions from the stem bark of Entada spiralis Ridl. against human dermatophytes and yeast-like fungus in vitro. Three types of human dermatophyte, Trichophyton mentagrophytes ATCC 9533, Microsporum gypseum ATCC 24102 and Trichophyton tonsurans ATCC 28942, and one yeast-like fungus, Candida glabrata ATCC 66032, were tested against the methanolic fractions labelled FA1, FA4 and FA5. T. mentagrophytes, T. tonsuran and M. gypseum were susceptible to all tested fractions in a concentration-dependent manner whereas C. glabrata was resistant. Fraction FA1 at a concentration of 400 mg/mL was found to exhibit the highest antifungal activity with the inhibition zone diameter of 22 mm (T. mentagrophytes). This fraction showed a minimum inhibitory concentration MIC of 0.097 mg/mL while the MIC value for the fraction FA4 and fraction FA5 was 3.12 mg/ml and 1.56 mg/ml respectively. Agar overlay bioautography assay results showed that most of the bioactive compounds were found in the fraction FA1. Based on these findings, it can be concluded that the stem bark extracts of E. spiralis can be a future source of potent natural antimicrobial drugs for superficial skin diseases.
    Matched MeSH terms: Candida glabrata
  12. Dual panel multiplex PCR assay for rapid detection of medically important fungi and resistant species of candida and aspergillus
    Jacinta Santhanam, Mohd Hanif Jainlabdin, Ang LC, Tzar Mohd Nizam
    Sains Malaysiana, 2018;47:489-498.
    Invasive fungal infections (IFIs) have risen dramatically in recent years among high risk immunocompromised patients.
    Rapid detection of fungal pathogens is crucial to timely and accurate antifungal therapy. Two multiplex polymerase
    chain reaction (PCR) assays were developed to detect major fungal species that cause invasive infections and identify
    resistant species. Genus specific primers for Candida, Aspergillus, Fusarium and species specific primers for Candida
    glabrata, Candida krusei and Aspergillus terreus which are known to be clinically resistant species, were designed from
    the internal transcribed spacer (ITS) regions of ribosomal ribonucleic acid (rRNA) gene complex. Both assays were
    performed simultaneously to promote rapid detection of fungal isolates based on distinct amplicon sizes. Inclusion of the
    universal fungal primers ITS 1 and ITS 4 in the genus specific assay produced a second amplicon for each isolate which
    served to confirm the detection of a fungal target. The limit of detection for the genus specific assay was 1 nanogram
    (ng) deoxyribonucleic acid (DNA) for Aspergillus fumigatus and Candida albicans, 0.1 ng DNA for Fusarium solani, while
    the species-specific assay detected 0.1 ng DNA of A. terreus and 10 picogram (pg) DNA of C. krusei and C. glabrata. The
    multiplex PCR assays, apart from universal detection of any fungal target, are able to detect clinically important fungi
    and differentiate resistant species rapidly and accurately, which can contribute to timely implementation of effective
    antifungal regime.
    Matched MeSH terms: Candida glabrata
  13. Epidemiology of candidemia and antifungal susceptibility in invasive Candida species in the Asia-Pacific region
    Wang H, Xu YC, Hsueh PR
    Future Microbiol, 2016 10;11:1461-1477.
    PMID: 27750452
    In the Asia-Pacific region, Candida albicans is the predominant Candida species causing invasive candidiasis/candidemia in Australia, Japan, Korea, Hong Kong, Malaysia, Singapore and Thailand whereas C. tropicalis is the most frequently encountered Candida species in Pakistan and India. Invasive isolates of C. albicans, C. parapsilosis complex and C. tropicalis remain highly susceptible to fluconazole (>90% susceptible). Fluconazole resistance (6.8-15%), isolates with the non-wild-type phenotype for itraconazole susceptibility (3.9-10%) and voriconazole (5-17.8%), and echinocandin resistance (2.1-2.2% in anidulafungin and 2.2% in micafungin) among invasive C. glabrata complex isolates are increasing in prevalence. Moreover, not all isolates of C. tropicalis have been shown to be susceptible to fluconazole (nonsusceptible rate, 5.7-11.6% in China) or voriconazole (nonsusceptible rate, 5.7-9.6% in China).
    Matched MeSH terms: Candida glabrata/drug effects; Candida glabrata/isolation & purification; Candida glabrata/pathogenicity
  14. Fulltext Assessment of Antifungal Activity of Bakuchiol on Oral-Associated Candida spp
    Nordin MA, Abdul Razak F, Himratul-Aznita WH
    Evid Based Complement Alternat Med, 2015;2015:918624.
    PMID: 26633986 DOI: 10.1155/2015/918624
    Bakuchiol is an active component of Psoralea glandulosa and Psoralea corylifolia, used in traditional Chinese medicine. The study aimed at investigating the antifungal activity of bakuchiol on planktonic and biofilm forms of orally associated Candida species. The antifungal susceptibility testing was determined by the broth micro dilution technique. Growth kinetics and cell surface hydrophobicity (CSH) of Candida were measured to assess the inhibitory effect of bakuchiol on Candida planktonic cells. Biofilm biomass and cellular metabolic activity were quantitatively estimated by the crystal violet (CV) and the 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assays. All Candida strains have been shown to be susceptible to bakuchiol with the MIC ranges from 12.5 to 100 μg/mL. Significant decrease in specific growth rates and viable counts demonstrates the inhibitory effect of bakuchiol on Candida planktonic cells. A brief exposure to bakuchiol also reduced CSH of Candida (P < 0.05), indicating altered surface properties of yeast cells towards hydrophobic interfaces. Biofilm biomass and cell metabolic activity were mostly decreased, except for C. glabrata (P = 0.29). The antifungal properties of bakuchiol on Candida species in this in vitro study may give insights into the application in therapeutic strategy against Candida infections.
    Matched MeSH terms: Candida glabrata
  15. Limosilactobacillus reuteri 29A Cell-Free Supernatant Antibiofilm and Antagonistic Effects in Murine Model of Vulvovaginal Candidiasis
    Boahen A, Chew SY, Neela VK, Than LTL
    Probiotics Antimicrob Proteins, 2023 Dec;15(6):1681-1699.
    PMID: 36881331 DOI: 10.1007/s12602-023-10050-0
    Vaginal dysbiosis advocates burgeoning of devious human vaginal pathobionts like Candida species that possess multiple virulence properties and metabolic flexibility to cause infections. Inevitably, antifungal resistance may emerge due to their innate nature (e.g., biofilm formation), which assists in their virulence as well as the formation of persister cells after dispersal. In consequence, the phenomenon of biofilm involvement in vulvovaginal candidiasis (VVC) and its recurrence is becoming paramount. Lactic acid bacteria and their derivatives have proven to be hostile to Candida species. Here, we throw more light on the potency of the derivatives, i.e., cell-free supernatant (CFS) produced by an indigenously isolated vaginal Lactobacillus strain, Limosilactobacillus reuteri 29A. In the present study, we investigated the antibiofilm and antagonistic effects of L. reuteri 29A CFS, against biofilms of Candida species and in murine model of vulvovaginal candidiasis. In our in vitro biofilm study, the CFS disrupted and inhibited preformed biofilms of C. albicans and C. glabrata. Scanning electron microscopy displayed the destruction of preformed biofilms and impediment of C. albicans morphogenesis by the CFS. Gas chromatography-mass spectrometry analysis showed multiple key compounds that may act singly or synergistically. In vivo, the CFS showed no collateral damage to uninfected mice; the integrity of infected vaginal tissues was restored by the administration of the CFS as seen from the cytological, histopathological, and electron microscopical analyses. The results of this study document the potential use of CFS as an adjuvant or prophylactic option in addressing vaginal fungal infections.
    Matched MeSH terms: Candida glabrata
  16. Increased expression and hotspot mutations of the multidrug efflux transporter, CDR1 in azole-resistant Candida albicans isolates from vaginitis patients
    Looi CY, D' Silva EC, Seow HF, Rosli R, Ng KP, Chong PP
    FEMS Microbiol Lett, 2005 Aug 15;249(2):283-9.
    PMID: 16006060
    The aims of our research were to investigate the gene expression of the multidrug efflux transporter, CDR1 and the major drug facilitator superfamily transporter, MDR1 gene in azole drug-resistant Candida albicans and Candida glabrata clinical isolates recovered from vaginitis patients; and to identify hotspot mutations that may be present in the C. albicans CaCDR1 gene that could be associated with drug-resistance. The relative expression of the CDR1 and MDR1 transcripts in ketoconazole and clotrimazole-resistant isolates and drug-susceptible ATCC strains were determined by semi-quantitative reverse transcription-polymerase chain reaction. Expression of CaCDR1 transcript was upregulated to varying extents in all three azole-resistant C. albicans isolates studied (1.6-, 3.7- and 3.9-fold) and all three C. glabrata isolates tested (at 1.9-, 2.3- and 2.7-fold). The overexpression level of CaCDR1 in the isolates correlated with the degree of resistance as reflected by the minimum inhibitory concentration (MIC) of the drugs. The messenger RNA for another efflux pump, MDR1, was also overexpressed in one of the azole-resistant C. albicans isolates that overexpressed CDR1. This finding suggests that drug-resistance may involve synergy between energy-dependent drug efflux pumps CDR1p and MDR1p in some but not all isolates. Interestingly, DNA sequence analysis of the promoter region of the CaCDR1 gene revealed several point mutations in the resistant clinical isolates compared to the susceptible isolates at 39, 49 and 151 nucleotides upstream from the ATG start codon. This finding provides new information on point mutations in the promoter region which may be responsible for the overexpression of CDR1 in drug-resistant isolates.
    Matched MeSH terms: Candida glabrata/genetics; Candida glabrata/isolation & purification*
  17. Fulltext Phylogenetic and Transcripts Profiling of Glucose Sensing Related Genes in Candida glabrata
    Ng TS, Mohd Desa MN, Sandai D, Chong PP, Than LT
    Jundishapur J Microbiol, 2015 Nov;8(11):e25177.
    PMID: 26855740 DOI: 10.5812/jjm.25177
    BACKGROUND: The sensing mechanism of glucose in Saccharomyces cerevisiae is well studied. However, such information is scarcely found in other yeast species such as Candida glabrata.

    OBJECTIVES: This study aimed to identify the glucose sensing pathway related genes of C. glabrata and to analyze the regulation pattern of these genes in response to different surrounding glucose concentrations through the quantitative real time polymerase chain reaction (qRT-PCR).

    MATERIALS AND METHODS: Phylogenetic analysis was carried out on predicted amino acid sequences of C. glabrata and S. cerevisiae to compare their degree of similarity. In addition, the growth of C. glabrata in response to different amounts of glucose (0%, 0.01%, 0.1%, 1% and 2%) was evaluated via the spot dilution assay on prepared agar medium. Besides, the SNF3 and RGT2, which act as putative glucose sensors, and the RGT1 and MIG1, which act as putative transcriptional regulators and selected downstream hexose transporters (HXTs), were analysed through qRT-PCR analysis for the gene expression level under different glucose concentrations.

    RESULTS: Comparative analysis of predicted amino acids in the phylogenetic tree showed high similarity between C. glabrata and S cerevisiae. Besides, C. glabrata demonstrated the capability to grow in glucose levels as low as 0.01% in the spot dilution assay. In qRT-PCR analysis, differential expressions were observed in selected genes when C. glabrata was subjected to different glucose concentrations.

    CONCLUSIONS: The constructed phylogenetic tree suggests the close evolutionary relationship between C. glabrata and S. cerevisiae. The capability of C. glabrata to grow in extremely low glucose environments and the differential expression of selected glucose-sensing related genes suggested the possible role of these genes in modulating the growth of C. glabrata in response to different glucose concentrations. This study helps deepen our understanding of the glucose sensing mechanism in C. glabrata and serves to provide fundamental data that may assist in unveiling this mechanism as a potential drug target.

    Matched MeSH terms: Candida glabrata
  18. Fulltext Microbiome of tracheoesophageal prosthesis: who are they?
    Syatirah Abdullah, Janet Quinn, Mohamed EL-Badawey, Nicholas Jakubovics
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):44-44.
    MyJurnal
    Introduction: Laryngectomy patients undergo voice rehabilitation that requires implantation of trachea-oesophagal speech valves (TESV). Usually, laryngeal cancer patients require insertion of these devices post-operatively to im-prove their quality of life. Implantation of TESV dates back to 1979 by pioneering work of Blom and Singer. There are cases of aspiration of TESV wearer reported, and obstruction of the TESV causes leakage through the valve and is suggested as a main reason for replacement of the device. The dysfunctional failure may be caused by microbial colonization on the valve or physical malfunction and requires immediate replacement is desirable. The aim of this study is to identify the microbial community members of selected TESVs using both culture-independent techniques (Next-generation sequencing) to analyse the microbiota, including unculturable species, and routine microbiology techniques (culture-dependent method) and to obtain representative isolates that can form the basis for experiments to enable increased understanding of the community. Methods: Biofilms were harvested from 16 explanted speech valves from patients visiting the ENT clinic in Freeman Hospital, Newcastle, UK. Routine microbiology techniques (culture-dependent method) including ChromeID® plates and Matrix-Assisted Laser Desorption/Ionization Time of Flight (MALDI-TOF) Mass Spectrometry were used for identification of TESV microbiome. Sequencing of the samples was performed at MR DNA (www.mrdnalab.com, USA) on a MiSeq following the manufacturer’s guidelines in order to determine the bacteria and candida composition in the biofilm community. Results: The most frequently isolated fungal species was C. albicans, which was cultured from 11 out of 16 TESVs (79%), followed by five TESVs with C. tropicalis (36%), three TESVs had C. glabrata (21%) and only one TESV contained S. cerevisiae (7%). Interestingly no biofilm communities contained more than two fungal species and 2 TESVs (12%) possessed only bacterial species. There were only 16 species of bacteria cultured and identified by MALDI-TOF MS. This was far lower than the 91 species that were detected by NGS. Species from the genus Lactobacillus were found in 10 of 16 TESVs (63%), the highest frequency of any bacterial genus isolated from TESVs followed by S. aureus found in eight TESVs of 16. S. epidermidis was identified in two TESVs (13%), Streptococcus spp., K. oxytoca and O. anthropi were both identified in five different TESVs, while the gut bacterium E. faecium was found in four TESVs. Only one TESV contained E. coli. Conclusion: TESV biofilm composition was dominated by Candida spp. and occasionally contained other types of eukaryote such as Saccharomycetes. It was not uncommon for more than one Candida species to be present. The biofilms also harboured a mixture of bacteria, with lactic acid producers (Lactobacillus sp. and Streptococcus sp.) normally accompanying Candida sp. in the biofilm.
    Matched MeSH terms: Candida glabrata
  19. Genetic diversity, antifungal susceptibility and enzymatic characterisation of Malaysian clinical isolates of Candida glabrata
    Lotfalikhani A, Khosravi Y, Sabet NS, Na SL, Ng KP, Tay ST
    Trop Biomed, 2018 Dec 01;35(4):1123-1130.
    PMID: 33601859
    Candida glabrata has been reported as the second or third most common yeast species isolated from patients with vaginitis and invasive candidiasis. This study was aimed to determine the genetic diversity, antifungal susceptibility and enzymatic profiles of C. glabrata isolated from vaginal and blood samples in the Medical Microbiology Diagnostic Laboratory, University Malaya Medical Centre. A random amplified polymorphic DNA (RAPD) analysis method, using M13 and (GTG)5 primers, was used for strain differentiation of C. glabrata isolates. Antifungal susceptibility testing of C. glabrata isolates was determined using E-test against amphotericin B, caspofungin, fluconazole and voriconazole and microbroth dilution method against clotrimazole. The enzymic profiles of C. glabrata were determined using APIZYM semi-quantitation kit and egg-yolk agar method. A total of 14 RAPD patterns were identified amongst C. glabrata isolates investigated this study. Susceptibility to amphotericin B, caspofungin, fluconazole and voriconazole was noted. Approximately one third of the isolates demonstrated resistance to clotrimazole (MIC>=1 µg/ml). A single isolate of C. glabrata was resistant to caspofungin (MIC:1.5 µg/ml). Enzymatic activities of acid and alkaline phosphatase, aminopeptidases, esterase and lipase and phospholipase were detected in the C. glabrata isolates. The genetic diversity and antifungal susceptibility profiles of C. glabrata isolates were presented in this study. Continued surveillance and monitoring of the incidence and antifungal resistance in C. glabrata isolates is necessary.
    Matched MeSH terms: Candida glabrata
  20. Fulltext Stem bark of Canarium Odontophyllum Miq. (dabai) as potential source of antimicrobial agent
    Noor Fazdilah Mustari, Zafira Ayushah Zainul Alamin, Noraziah Mohammad Zin, Dayang Fredalina Basri
    Jurnal Sains Kesihatan Malaysia, 2017;15(1):1-6.
    MyJurnal
    The objective of this study was to evaluate the antimicrobial potential of methanol, acetone and distilled water stem
    bark extracts from Canarium odontophyllum against Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 6633,
    Escherichia coli ATCC 25932, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii strain sensitive, Candida
    albicans ATCC 64677, Candida glabrata ATCC 90028, Aspergillus niger and Fusarium solani M2781. The extracts from
    C. odontophyllum stem bark from 3.125 mg/ml to 25 mg/ml were screened against the tested microorganisms using disc
    diffusion method. The Minimum inhibitory concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the
    extracts against susceptible organisms were determined using microbroth dilution method and streak-plate technique,
    respectively. From the antibacterial screening assay, the growth of S. aureus, B. cereus and A. baumannii were inhibited
    by methanol extract whereas the acetone extract was capable of inhibiting all the tested microorganisms except E.coli,
    F. solani and A. niger. The lowest MIC value for methanol extract was against A. baumannii (0.195 mg/ml) whereas
    its MBC value was twice its MIC value (0.391 mg/ml), indicating that methanol extract was bacteriostatic against A.
    baumannii. While for acetone extract, S. aureus showed bactericidal effect with equal MIC and MBC values at 0.195 mg/
    ml. In conclusion, stem bark of C. odontophyllum has the potential to be the source of antibacterial agent and can be
    exploited as an alternative phytoantimicrobial.
    Matched MeSH terms: Candida glabrata
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