Trichophyton rubrum is a common pathogenic fungal species that is responsible for causing infection on
human skin, hair and nail. The antifungal-resistant strains complicate the treatment regime.
Hydroxychavicol (HC) is one of the main compounds from Piper betel leaf that have antifungal potential and
its mechanism of action has not been studied yet. The objective of this preliminary study to determine the
antifungal properties of HC against T. rubrum using transmission electron microscope (TEM) on gross and
ultrastructure of T. rubrum hypha. T. rubrum was treated with HC and miconazole (MI) at concentrations of
1.25, 2.5, 5 and 10 mg/mL for 1, 3, 5 and 7 days continuously. Generally, fungi structures became more
severely damaged at increasing treatment duration. Microscopically, the fungi’s cell wall treated with HC
showed a rough surface, shrinkage and demolition similar to the MI treated group. The fungi organelles were
also demolished and disorganized. This study revealed that HC has the ability to inhibit T. rubrum growth
and has potential to be an antifungal agent for skin infections.
Micafungin was reported to be non-inferior to liposomal amphotericin B (LAmB) in treating patients with candidaemia and invasive candidiasis (IC). The current study aimed to evaluate the economic impact of using micafungin versus LAmB for treatment of candidaemia and IC in Turkey. A decision analytic model, which depicted economic consequences upon administration of micafungin or LAmB for treating patients with candidaemia and IC in the Turkish hospitals, was constructed. Patients were switched to an alternative antifungal agent if initial treatment failed due to mycological persistence. All patients were followed up until treatment success or death. Outcome probabilities were obtained from published literature and cost inputs were derived from the latest Turkish resources. Expert panels were used to estimate data that were not available in the literature. Cost per patient treated for each intervention was then calculated. Sensitivity analyses including Monte Carlo simulation were performed. For treatment of candidaemia and IC, micafungin (€4809) was associated with higher total cost than LAmB (€4467), with an additional cost of €341 per treated patient. Cost of initial antifungal treatment was the major cost driver for both comparators. The model outcome was robust over a wide variation in input variables except for drug acquisition cost and duration of initial antifungal treatment with micafungin or LAmB. LAmB is cost-saving relative to micafungin for the treatment of candidaemia and IC from the Turkish hospital perspective, with variation in drug acquisition cost of the critical factor affecting the model outcome.
Effect of 2.0 % ginger oil (GO) and 1.5 % ginger extract (GE) in combination with 10.0 % gum arabic (GA) was evaluated for the postharvest control of anthracnose and maintaining quality of Eksotika II papaya fruit during storage at 12 ± 1 °C and 80-85 % RH. Antifungal compounds present in GO and GE were analyzed using gas chromatography and GO was found to contain α-pinene, 1, 8-cineole and borneol, while only borneol was present in GE due to different extraction methods applied. The highest antifungal activity was shown in 2.0 % GO combined with 10 % GA, which significantly (P
This study aimed to examine the anti-candidal efficacy of a novel ketone derivative isolated from Diaporthe sp. ED2, an endophytic fungus residing in medicinal herb Orthosiphon stamieus Benth. The ethyl acetate extract of the fungal culture was separated by open column and reverse phase high-performance liquid chromatography (HPLC). The eluent at retention time 5.64 min in the HPLC system was the only compound that exhibited anti-candidal activity on Kirby-Bauer assay. The structure of the compound was also elucidated by nuclear magnetic resonance and spectroscopy techniques. The purified anti-candidal compound was obtainedas a colorless solid and characterized as 3-hydroxy-5-methoxyhex-5-ene-2,4-dione. On broth microdilution assay, the compound also exhibited fungicidal activity on a clinical strain of Candida albicans at a minimal inhibitory concentration of 3.1 μg/ml. The killing kinetic analysis also revealed that the compound was fungicidal against C. albicans in a concentration- and time-dependent manner. The compound was heat-stable up to 70°C, but its anti-candidal activity was affected at pH 2.
Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.
Atratoxin B1 which was extracted from a local sea cucumber, Holothuria atra is a potential antifungal agent against dermatophytes. Exposure of Microsporum canis mycelia inoculated into Sabouraud glucose agar medium to the 10 mg/ml atratoxin B1 solution, resulted in complete suppression of the fungal growth. Prolonged exposure to the atratoxin B] (72 hours) resulted with necrosis in a substantial portion of the existing hyphae. The main anomalies noted were the abnormally shaped hyphae and the alterations in its morphology and cytology.
Atratoksin B] yang diekstrak daripada timun laut tempatan, Holothuria atra, adalah suatu agen antikulat yang berpotensi terhadap dermatofit. Pendedahan miselium Microsporum canis yang diinokulat ke dalam medium agar glukosa Sabouraud kepada larutan atratoksin B] berkepekatan 10 mg/ml, mengakibatkan penindasan lengkap dalam pertumbuhannya. Pendedahan yang lebih lama kepada larutan atratoksin B] (72 jam) mengakibatkan nekrosis berlaku pada sebahagian besar hifanya. Keganjilan yang jelas berlaku adalah ketidaknormalan pada bentuk hifanya dan juga pengubahsuaian yang terjadi pada morfologi dan sitologinya.
A study was conducted to determine the prevalence of fungal infection in cancer patients warded at the Hospital Kuala Lumpur. There were 138 patients included in the study: 74 with haematological malignancies and 64 with solid tumours. Serological results showed that for candidiasis 16/138 (11.5%) and 10/134 (7.5%) were greater than 1:8 reactive for antigen and antibodies respectively. For aspergillosis, 29/122 (23.8%) sera were antigen reactive. Only 1/133 each (O.SO/o) was reactive for cryptococcal antigen and antibody. The types of malignancies, the age of the patient, a history of neutropenia, the duration of the cancer, the number of courses of chemotherapy or radiotherapy were not predictive of fungal infections. In view of the high serological evidence of fungal infection and the lack of a reliable diagnostic test, empirical antifungal treatment must be considered in all febrile neutropenic cancer patients.
Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.
In the presented work, 2,3-dihydro-1,4-benzodioxin-6-amine (1) was reacted with 4-chlorobenzenesulfonyl chloride (2) in presence of aqueous basic aqueous medium to obtain 4-chloro-N-(2,3-dihydro-1,4-benzodioxin-6-yl)benzenesulfonamide (3). In parallel, various un/substituted anilines (4a-l) were treated with bromoacetyl bromide (5) in basified aqueous medium to obtain corresponding 2-bromo-N-(un/substituted)phenylacetamides (6a-l) as electrophiles. Then the compound 3 was finally reacted with these electrophiles, 6a-l, in dimethylformamide (DMF) as solvent and lithium hydride as base and activator to synthesize a variety of 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(un/substituted)phenylacetamides (7a-l). The synthesized compounds were corroborated by IR, 1H-NMR and EI-MS spectral data for structural confirmations. These molecules were then evaluated for their antimicrobial and antifungal activities along with their %age hemolytic activity. Some compounds were found to have suitable antibacterial and antifungal potential, especially the compound 2-[[(4-chlorophenyl)sulfonyl](2,3-dihydro-1,4-benzodioxin-6-yl)amino]-N-(3,5-dimethylphenyl)acetamide (7l) exhibited good antimicrobial potential with low value of % hemolytic activity.
The present study aimed to examine the chemical compositions of the essential oils of Beilschmiedia madang and their antioxidant, antibacterial, antifungal, anticholinesterase and anti-tyrosinase activities. The major constituents of the essential oils of leaf and bark of B. madang were δ-cadinene (17.0 and 20.5 %), β-caryophyllene (10.3 and 6.7 %), α-cubebene (11.3 and 15.6 %), and α-cadinol (5.8 and 10.6 %). The essential oils were screened for their antioxidant activities using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, β-carotene/linoleic acid bleaching, and total phenolic content. The bark oil showed the highest β-carotene/linoleic acid bleaching (90.3 % ± 0.2) and DPPH radical scavenging (IC50 212.0 µg/mL), while the highest phenolic content was exhibited by the leaf oil (94.5 % ± 0.3 mg GA/g). The antibacterial and antifungal activities were investigated by the disc diffusion and micro dilution method. The leaf and bark oils showed moderate activity towards Bacillus subtilis and Staphylococcus aureus with minimum inhibitory concentration (MIC) value 125 µg/mL. For antifungal assay, the bark oil showed strong activity towards Aspergillus niger and Aspergillus fumigatus with MIC value 62.5 µg/mL. Anticholinesterase and anti-tyrosinase activities were evaluated against Ellman method and mushroom tyrosinase, respectively. The results showed that leaf oil gave significant percentage inhibition (I%: acetylcholinesterase 55.2 %, butyrylcholinesterase 60.4 %, tyrosinase 53.1 %).
The immune system is an intricate and coordinated nexus serving as a natural defense to preclude internal and external pathogenic insults. The deregulation in the natural balance of immunological functions as a consequence of either over expression or under expression of immune cells tends to cause disruption of homeostasis in the body and may lead to development of numerous immune system disorders. Chalcone moieties (1,3-diphenyl-2-propen-1-one) have been well-documented as ideal lead compounds or precursors to design a wide range of pharmacologically active agents to down-regulate various immune disorders. Owing to their unique structural and molecular framework, these α, β-unsaturated carbonyl-based moieties have also gained remarkable recognition due to their other multifarious pharmacological properties including antifungal, anti-inflammatory, anti-malarial, antibacterial, anti-tuberculosis, and anticancer potential. Though a great number of methodologies are currently being employed for their synthesis, this review mainly focuses on the natural and synthetic chalcone derivatives that are exclusively synthesized via Claisen-Schmidt condensation reaction and their immunomodulatory prospects. We have critically reviewed the literature and provided convincing evidence for the promising efficacy of chalcone derivatives to modulate functioning of various innate and adaptive immune players including granulocytes, mast cells, monocytes, macrophages, platelets, dendritic cells, natural killer cells, and T-lymphocytes.
To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1), multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time quantitative PCR (RT-qPCR) analysis, given the known interaction of the corresponding proteins with antifungals and with the efflux blocker FK506. The expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2-4 times higher in the TRF-resistant strain grown in the presence of 0.14 µg/mL of TRF than in TRF-susceptible strains cultured in the absence of TRF. The TRF-resistant strain exhibited MICs of > 32 µg/mL for TRF alone; this resistance was attenuated to an MIC of 8 µg/mL in the presence of FK506, indicating that the TRF inhibitory concentration index value was
This study discusses the isolation and identification of a new Streptomycetes highly active chitinase producer. Fifteen strains were isolated from Malaysian soil samples. The isolate WICC-A03 was found to be the most active chitinase producer. Its antifungal activity was evaluated against many phytopathogens. The identification of WICC-A03 using phenotypic and genotypic methods strongly indicated that strain WICC-A03 belonged to the genus Streptomyces and displayed similarity (91%) with Streptomyces glauciniger. Thus, it was given the suggested name S. glauciniger WICC-A03 with accession number: JX139754. WICC-A03 produces extracellular chitinase in a medium containing 1.5% colloidal chitin in submerged culture on 144 h. The produced enzyme was partially characterised and its molecular weight of 50 kDa was determined by using SDS-PAGE. This study indicates that WICC-A03 is a potential chitinase producer for biocontrol of plant pathogens. Further experiments are being carried out to optimise medium composition and cultivation conditions under lab and bioreactor scale.
Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis.
We aimed to investigate the effects that natural lipids, theobroma oil (TO) and beeswax (BW), might have on the physical properties of formulated nanoparticles and also the degree of expulsion of encapsulated amphotericin B (AmB) from the nanoparticles during storage. Lecithin and sodium cholate were used as emulsifiers whilst oleic acid (OA) was used to study the influence of the state of orderliness/disorderliness within the matrices of the nanoparticles on the degree of AmB expulsion during storage. BW was found to effect larger z-average diameter compared with TO. Lecithin was found to augment the stability of the nanoparticles imparted by BW and TO during storage. An encapsulation efficiency (%EE) of 59% was recorded when TO was the sole lipid as against 42% from BW. In combination however, the %EE dropped to 39%. When used as sole lipid, TO or BW formed nanoparticles with comparatively higher enthalpies, 21.1 and 23.3 J/g respectively, which subsequently caused significantly higher degree of AmB expulsion, 81 and 83% respectively, whilst only 11.8% was expelled from a binary TO/BW mixture. A tertiary TO/BW/OA mixture registered the lowest enthalpy at 8.07 J/g and expelled 12.6% of AmB but encapsulated only 22% of AmB. In conclusion, nanoparticles made from equal concentrations of TO and BW produced the most desirable properties and worthy of further investigations.
Penicillium marneffei is a dimorphic fungus which commonly causes a life threatening systemic fungal infection in an immunocompromised host. It has been recognized as an AIDS defining illness in Malaysia since the beginning of the HIV pandemic. The presence of various non specific clinical presentations, especially the characteristic umbilicated papular rashes with central necrosis which lead to significant ill health in immunocompromised patients should alarm clinicians to the possibility of Penicillium marneffei infection and prompt investigations accordingly. Simple investigations like blood culture and fungal staining of the skin scrapping can confirm the diagnosis in the majority of cases. Early treatment with appropriate systemic antifungal for a definite duration will significantly decrease the mortality rate from penicilliosis.
Matched MeSH terms: Antifungal Agents/therapeutic use
Ganoderma (G.) boninense is a white rot fungus, which can be found in the palm oil tree. Several studies have shown that G. boninense has antimicrobial and antagonistic properties. However, there is limited information reported on antifungal properties especially on Candida (C) albicans. Hence, this study was conducted to determine the anti-Candida activity of G. boninense against C albicans.
The purpose of this study was to investigate the activity of xanthorrhizol isolated from Curcuma xanthorrhiza Roxb. on Candida albicans biofilms at adherent, intermediate, and mature phase of growth. C. albicans biofilms were formed in flat-bottom 96-well microtiter plates. The biofilms of C. albicans at different phases of development were exposed to xanthorrhizol at different concentrations (0.5 µg/mL-256 µg/mL) for 24 h. The metabolic activity of cells within the biofilms was quantified using the XTT reduction assay. Sessile minimum inhibitory concentrations (SMICs) were determined at 50% and 80% reduction in the biofilm OD₄₉₀ compared to the control wells. The SMIC₅₀ and SMIC₈₀ of xanthorrhizol against 18 C. albicans biofilms were 4--16 µg/mL and 8--32 µg/mL, respectively. The results demonstrated that the activity of xanthorrhizol in reducing C. albicans biofilms OD₄₉₀ was dependent on the concentration and the phase of growth of biofilm. Xanthorrhizol at concentration of 8 µg/mL completely reduced in biofilm referring to XTT-colorimetric readings at adherent phase, whereas 32 µg/mL of xanthorrhizol reduced 87.95% and 67.48 % of biofilm referring to XTT-colorimetric readings at intermediate and mature phases, respectively. Xanthorrhizol displayed potent activity against C. albicans biofilms in vitro and therefore might have potential therapeutic implication for biofilm-associated candidal infections.
Hevea brasiliensis extracts could potentially be employed as a relatively low cost resource for various anti-fungal activities due to the simplicity of the extract preparation and its abundance especially in the tropical region. Latex B-serum was reported to have anti-cancer property and its specificity in anti-fungal property has not been elucidated. The present study was conducted to determine the anti-fungal activity of Hevea latex B-serum against Candida (C.) albicans (a rounded cell fungus) and Aspergillus (A.) niger (a filamentous fungus).
Sporotrichosis is a subacute or chronic fungal infection caused by the ubiquitous fungus Sporothrix schenckii. Disseminated cutaneous sporotrichosis is an uncommon entity and is usually present in the immunosuppressed. Here, a case of disseminated cutaneous sporotrichosis in an immunocompetent patient is reported. This 70-year-old healthy woman presented with multiple painful ulcerated nodules on her face and upper and lower extremities of 6-month duration, associated with low-grade fever, night sweats, loss of appetite, and loss of weight. Histopathological examination of the skin biopsy revealed epidermal hyperplasia and granulomatous inflammation in the dermis, with budding yeast. Fungal culture identified S. schenckii. She had total resolution of the lesions after 2 weeks of intravenous amphotericin B and 8 months of oral itraconazole. All investigations for underlying immunosuppression and internal organ involvement were negative. This case reiterates that disseminated cutaneous sporotrichosis, although common in the immunosuppressed, can also be seen in immunocompetent patients.
Matched MeSH terms: Antifungal Agents/therapeutic use