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Whole genome sequencing analysis demonstrates therapy-induced echinocandin resistance in Candida auris isolates

Spruijtenburg B, Ahmad S, Asadzadeh M, Alfouzan W, Al-Obaid I, Mokaddas E, et al.

Mycoses, 2023 Dec;66(12):1079-1086.
PMID: 37712885 DOI: 10.1111/myc.13655

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra-patient resistance development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin-resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17-127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1-10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin-resistant strains are capable of long-term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross-infect other patients, or remain viable for longer time periods in the hospital environment.

Matched MeSH terms: Antifungal Agents/pharmacology; Antifungal Agents/therapeutic use
Fulltext Antifungal effect of Malaysian neem leaf extract on selected fungal species causing otomycosis in in-vitro culture medium

Puvan Arul Arumugam, Irfan Mohamad, Rosdan Salim, Zeehaida Mohamed

Malaysian Journal of Medicine and Health Sciences, 2015;11(2):69-84.
MyJurnal

Azadirachta indica (neem) has been used for a long time in agricultural and alternative medicine. Neem
had been proved effective against certain fungi that could infect human body. This pilot study aims to
demonstrate the antifungal effect of Malaysian neem leaf extracts on the pathogenic fungi in otomycosis,
Aspergillus niger and Candida albicans. This is a laboratory-controlled prospective study conducted at
Universiti Sains Malaysia. The powder form of Malaysian neem leaf was prepared. Ethanol and aqueous
extracts of the neem leaf was diluted with sterile water to establish five different concentrations of 50 g/
ml, 25 g/ml, 12.5 g/ml, 6.25 g/ml and 3.125g/ml. The extract was tested on Sabouraud Dextrose Agar
suspended with Candida albicans and Aspergillus niger respectively. Well diffusion method was used
and zone of inhibition was measured. Growth of the fungi was inhibited in both alcohol and aqueous
extract concentrations. The minimum inhibitory concentration (MIC) of Malaysian neem aqueous extract
against Candida albicans was 11.91 g/ml, neem ethanol extract against Candida albicans was 5.16 g/
ml, neem aqueous extract against Aspergillus niger was 7.73 g/ml and neem ethanol extract against
Aspergillus niger was 9.25 g/ml. Statistical analysis showed that the antifungal activity of Candida
albicans is better in alcohol neem than aqueous extract (p

Matched MeSH terms: Antifungal Agents
Fulltext A review on antibacterial, antiviral, and antifungal activity of curcumin

Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K

Biomed Res Int, 2014;2014:186864.
PMID: 24877064 DOI: 10.1155/2014/186864

Curcuma longa L. (Zingiberaceae family) and its polyphenolic compound curcumin have been subjected to a variety of antimicrobial investigations due to extensive traditional uses and low side effects. Antimicrobial activities for curcumin and rhizome extract of C. longa against different bacteria, viruses, fungi, and parasites have been reported. The promising results for antimicrobial activity of curcumin made it a good candidate to enhance the inhibitory effect of existing antimicrobial agents through synergism. Indeed, different investigations have been done to increase the antimicrobial activity of curcumin, including synthesis of different chemical derivatives to increase its water solubility as well ass cell up take of curcumin. This review aims to summarize previous antimicrobial studies of curcumin towards its application in the future studies as a natural antimicrobial agent.

Matched MeSH terms: Antifungal Agents/pharmacology*
Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes

Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA

J Toxicol, 2009;2009:912320.
PMID: 20130764 DOI: 10.1155/2009/912320

Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.

Matched MeSH terms: Antifungal Agents
Enhancement of anti-candidal activity of endophytic fungus Phomopsis sp. ED2, isolated from Orthosiphon stamineus Benth, by incorporation of host plant extract in culture medium

Yenn TW, Lee CC, Ibrahim D, Zakaria L

J Microbiol, 2012 Aug;50(4):581-5.
PMID: 22923105 DOI: 10.1007/s12275-012-2083-8

This study examined the effect of host extract in the culture medium on anti-candidal activity of Phomopsis sp. ED2, previously isolated from the medicinal herb Orthosiphon stamineus Benth. Interestingly, upon addition of aqueous host extract to the culture medium, the ethyl acetate extract prepared from fermentative broth exhibited moderate anti-candidal activity in a disc diffusion assay. The minimal inhibitory concentration of this extract was 62.5 μg/ml and it only exhibited fungistatic activity against C. albicans. In the time-kill study, a 50% growth reduction of C. albicans was observed at 31.4 h for extract from the culture incorporating host extract. In the bioautography assay, only one single spot (Rf 0.59) developed from the extract exhibited anti-candidal activity. A spot with the a similar Rf was not detected for the crude extract from YES broth without host extract. This indicated that the terpenoid anti-candidal compound was only produced when the host extract was introduced into the medium. The study concluded that the incorporation of aqueous extract of the host plant into the culture medium significantly enhanced the anti-candidal activity of Phomopsis sp. ED2.

Matched MeSH terms: Antifungal Agents/isolation & purification; Antifungal Agents/metabolism*
QSAR classification model for diverse series of antifungal agents based on binary coyote optimization algorithm

Al-Fakih AM, Qasim MK, Algamal ZY, Alharthi AM, Zainal-Abidin MH

SAR QSAR Environ Res, 2023 Apr;34(4):285-298.
PMID: 37157994 DOI: 10.1080/1062936X.2023.2208374

One of the recently developed metaheuristic algorithms, the coyote optimization algorithm (COA), has shown to perform better in a number of difficult optimization tasks. The binary form, BCOA, is used in this study as a solution to the descriptor selection issue in classifying diverse antifungal series. Z-shape transfer functions (ZTF) are evaluated to verify their efficiency in improving BCOA performance in QSAR classification based on classification accuracy (CA), the geometric mean of sensitivity and specificity (G-mean), and the area under the curve (AUC). The Kruskal-Wallis test is also applied to show the statistical differences between the functions. The efficacy of the best suggested transfer function, ZTF4, is further assessed by comparing it to the most recent binary algorithms. The results prove that ZTF, especially ZTF4, significantly improves the performance of the original BCOA. The ZTF4 function yields the best CA and G-mean of 99.03% and 0.992%, respectively. It shows the fastest convergence behaviour compared to other binary algorithms. It takes the fewest iterations to reach high classification performance and selects the fewest descriptors. In conclusion, the obtained results indicate the ability of the ZTF4-based BCOA to find the smallest subset of descriptors while maintaining the best classification accuracy performance.

Matched MeSH terms: Antifungal Agents*
Fulltext Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing

Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al.

ACS Omega, 2021 Mar 30;6(12):8210-8225.
PMID: 33817480 DOI: 10.1021/acsomega.0c06242

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.

Matched MeSH terms: Antifungal Agents
Liquid chromatographic method for the determination of plasma itraconazole and its hydroxy metabolite in pharmacokinetic/bioavailability studies

Wong JW, Nisar UR, Yuen KH

J Chromatogr B Analyt Technol Biomed Life Sci, 2003 Dec 25;798(2):355-60.
PMID: 14643517

A sensitive and selective high-performance liquid chromatographic method was developed for the determination of itraconazole and its active metabolite, hydroxyitraconazole, in human plasma. Prior to analysis, both compounds together with the internal standard were extracted from alkalinized plasma samples using a 3:2 (v/v) mixture of 2,2,4-trimethylpentane and dichloromethane. The mobile phase comprised 0.02 M potassium dihydrogen phosphate-acetonitrile (1:1, v/v) adjusted to pH 3.0. Analysis was run at flow-rate of 0.9 ml/min with excitation and emission wavelengths set at 260 and 365 nm, respectively. Itraconazole was found to adsorb on glass or plastic tubes, but could be circumvented by prior treating the tubes using 10% dichlorodimethylsilane in toluene. Moreover, rinsing the injector port with acetonitrile helped to overcome any carry-over effect. This problem was not encountered with hydroxyitraconazole. The method was sensitive with limit of quantification of 3 ng/ml for itraconazole and 6 ng/ml for hydroxyitraconazole. The calibration curve was linear over a concentration range of 2.8-720 ng/ml for itraconazole and 5.6-720 ng/ml for the hydroxy metabolite. Mean recovery value of the extraction procedure for both compounds was about 85%, while the within-day and between-day coefficient of variation and percent error values of the assay method were all less than 15%. Hence, the method is suitable for use in pharmacokinetic and bioavailability studies of itraconazole.

Matched MeSH terms: Antifungal Agents/blood*; Antifungal Agents/pharmacokinetics
Fulltext Usage and completeness of antimicrobial prescribing form within general intensive care unit in a tertiary hospital

Nordin N. N., Lau, C. L., Wan Mat W. R., Yow, H. Y.

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):3-3.
MyJurnal

Introduction: The incidence of antimicrobial resistance (AMR) has increased worldwide including Malaysia, which may be attributed partly to inappropriate prescribing of antimicrobials. Antimicrobial prescribing form has been introduced to mandate appropriate antimicrobial prescription including documented indication as a key standard of antimicrobial stewardship practice. Hence, this current study aimed to determine the usage and completeness of the designated antimicrobial prescribing form that had been implemented in the General Intensive Care Unit (GICU), Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Methods: This prospective observational study was carried out in GICU UKMMC from 30 August 2018 to 30 November 2018 by convenience sampling. The information that was recorded in the antimicrobial prescribing form was collected by using the designated data collection form. A total of 68 patients were included and 205 antimicrobial prescribing forms were evaluated. Results: There were 100% usage of antimicrobial prescribing forms found in this study. However, only 81 ± 8 % of these forms were completely filled. Indication for the antimicrobial prescription was not filled in 47% of the forms. Almost two thirds of the antimicrobial prescriptions were empirically indicated and one percent de-escalation of antimicrobial therapy was filled in the forms. These prescriptions comprised of 91.7% antibiotics, 7.8% antifungals and 0.5% antivirals. The suspected site of infections were primarily from the lungs (27%), gastrointestinal (16%), blood (16%) and central nervous system (14%). Piperacillin/Tazobactam was the most frequent antibiotic prescribed (21%), followed by third and fourth generation cephalosporins (20%). Conclusion: This study provided an overview of the uptake of the antimicrobial prescribing form implementation and highlighted the requirement for supplementary efforts to maximize the compliance of this form.

Matched MeSH terms: Antifungal Agents
Effects of phenolic monomers on the enzymes activities and volatile fatty acids production of Neocallimastix frontalis B9

Zuhainis Saad W, Abdullah N, Alimon AR, Yin Wan H

Anaerobe, 2008 Apr;14(2):118-22.
PMID: 18083606

The effects of phenolic monomers (i.e. rho-coumaric acid, ferulic acid, rho-hydroxybenzaldehyde and vanillin) on the enzymes and fermentation activities of Neocallimastix frontalis B9 grown in ball-milled filter paper and guinea grass media were studied. The enzymes studied were carboxymethylcellulase (CMCase), filterpaperase (FPase), xylanase and beta-glucosidase. At 96 h of incubation, N. frontalis grown in ball-milled filter paper medium produced comparable xylanase and CMCase activities (0.41, 0.5 micromol/min/mg protein) while in guinea grass medium, N. frontalis produced higher xylanase activity than that of CMCase activity (2.35, 0.05 micromol/min/mg protein). The other enzymes activities were low. When N. frontalis was grown in ball-milled filter paper medium, only acetic acid was produced. However, when grown in guinea grass medium, the major end-product was acetate, but propionic, butyric and isovaleric were also produced in lesser amount. Vanillin showed the least inhibitory effects to enzyme activities of N. frontalis B9 grown in both ball-milled filter paper and guinea grass media. For total volatile fatty acid production, all phenolic monomers showed inhibitory effects, but rho-coumaric and ferulic acids were the stronger inhibitors than rho-hydroxybenzaldehyde and vanillin.

Matched MeSH terms: Antifungal Agents/pharmacology*
Chemical compositions and biological activities of the essential oils of Beilschmiedia madang Blume (Lauraceae)

Salleh WM, Ahmad F, Yen KH

Arch Pharm Res, 2015 Apr;38(4):485-93.
PMID: 25098422 DOI: 10.1007/s12272-014-0460-z

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 %).

Matched MeSH terms: Antifungal Agents/isolation & purification; Antifungal Agents/pharmacology; Antifungal Agents/chemistry
A serological survey to determine the prevalence of fungal infection in cancer patients at the Hospital Kuala Lumpur

Cheong I, Tan SC, Wong WH, Zainuddin RH, Yassin MS

Family Physician, 1994;6:9-11.

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.

Matched MeSH terms: Antifungal Agents
Fulltext Disseminated cutaneous sporotrichosis in an immunocompetent individual

Yap FB

Int J Infect Dis, 2011 Oct;15(10):e727-9.
PMID: 21719337 DOI: 10.1016/j.ijid.2011.05.005

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
Chromoblastomycosis in Sarawak, East malaysian Borneo

Yap FB

Trans R Soc Trop Med Hyg, 2010 Feb;104(2):168-9.
PMID: 19766279 DOI: 10.1016/j.trstmh.2009.05.016

A retrospective study was conducted to determine the clinical characteristics and treatment outcomes of 11 new patients with a histological diagnosis of chromoblastomycosis at Sarawak General Hospital, Malaysia, between 1996 and 2008. The majority (81.8%) were males, and the median age at presentation was 40 years. Over half the patients were farmers. All the patients had irregular verrucous lesions, mostly on the lower limbs (90.9%), and had initially been misdiagnosed. The mean duration of the lesions was 13.8 years. Oral terbinafine and itraconazole were administered to all the patients; clinical cure was seen in 54.5%, and partial response in 18.2%. Concomitant electrocautery and cryotherapy were only effective for small lesions.

Matched MeSH terms: Antifungal Agents/therapeutic use
Fulltext Chromoblastomycosis

Yap FB

Int J Infect Dis, 2010 Jun;14(6):e543-4.
PMID: 19889559 DOI: 10.1016/j.ijid.2009.07.005
Matched MeSH terms: Antifungal Agents/administration & dosage
Inhibitory Mechanism of Flavonoids from Sedum aizoon L. on Rhizopus nigricans

Ge Q, Wang K, Shao X, Wei Y, Zhang X, Liu Y, et al.

Foodborne Pathog Dis, 2023 May;20(5):197-208.
PMID: 37172299 DOI: 10.1089/fpd.2022.0083

Rhizopus nigricans is a widespread phytopathogen in fruits and vegetables that can cause considerable economic effects and resource waste. Flavonoids from Sedum aizoon L. (FSAL) have specific antifungal activities. This study selected FSAL as an antifungal to prolong the preservation of fruits and vegetables. The results showed that the mycelial morphology and ultrastructure were damaged by the FSAL treatment (1.0 minimum inhibitory concentration), led to the increase of reactive oxygen species and malondialdehyde, and affected the activity of key enzymes in the glycolytic pathway, such as lactic dehydrogenase, pyruvate kinase, and hexokinase of R. nigricans. Key genes in glycolysis were upregulated or downregulated. In addition, in the treatment and control groups, 221 differentially expressed genes were found, including 89 that were upregulated and 32 that were downregulated, according to the transcriptome results. The differential genes were mainly enriched in glycolysis, pyruvate metabolism, and citrate cycle pathways. The results revealed some insights into the antifungal mechanism of FSAL against R. nigricans and offered a theoretical foundation for its advancement as a novel plant-derived antifungal agent.

Matched MeSH terms: Antifungal Agents/pharmacology
Fulltext Genome-Wide Transcription Study of Cryptococcus neoformans H99 Clinical Strain versus Environmental Strains

Movahed E, Munusamy K, Tan GM, Looi CY, Tay ST, Wong WF

PLoS One, 2015;10(9):e0137457.
PMID: 26360021 DOI: 10.1371/journal.pone.0137457

The infection of Cryptococcus neoformans is acquired through the inhalation of desiccated yeast cells and basidiospores originated from the environment, particularly from bird's droppings and decaying wood. Three environmental strains of C. neoformans originated from bird droppings (H4, S48B and S68B) and C. neoformans reference clinical strain (H99) were used for intranasal infection in C57BL/6 mice. We showed that the H99 strain demonstrated higher virulence compared to H4, S48B and S68B strains. To examine if gene expression contributed to the different degree of virulence among these strains, a genome-wide microarray study was performed to inspect the transcriptomic profiles of all four strains. Our results revealed that out of 7,419 genes (22,257 probes) examined, 65 genes were significantly up-or down-regulated in H99 versus H4, S48B and S68B strains. The up-regulated genes in H99 strain include Hydroxymethylglutaryl-CoA synthase (MVA1), Mitochondrial matrix factor 1 (MMF1), Bud-site-selection protein 8 (BUD8), High affinity glucose transporter 3 (SNF3) and Rho GTPase-activating protein 2 (RGA2). Pathway annotation using DAVID bioinformatics resource showed that metal ion binding and sugar transmembrane transporter activity pathways were highly expressed in the H99 strain. We suggest that the genes and pathways identified may possibly play crucial roles in the fungal pathogenesis.

Matched MeSH terms: Antifungal Agents/pharmacology
New compounds with antimicrobial activities from Elaeodendron buchananii stem bark

Odak JA, Manguro LOA, Wong KC

J Asian Nat Prod Res, 2018 Jun;20(6):510-524.
PMID: 29338355 DOI: 10.1080/10286020.2017.1420648

The plant species Elaeodendron buchananii Loes is widely used in folklore medicine to manage microbial infections in Kenya. Previous studies on the plant fruits and root bark revealed the presence of steroids and terpenoids. The present phytochemical analysis of the plant stem bark has led to the isolation of four new triterpenes characterized as methyl 3β-acetoxy-11α, 19α, 28-trihydroxyurs-12-en-23-oic acid (1), 3β, 11α, 19α-trihydroxyurs-12-en-23, 28-dioic acid (2), 3β-acetoxy-19α, 23, 28-trihydroxyurs-12-ene (3) and 3-oxo-19α, 28-dihydroxyurs-12-en-24-oic acid (4), together with ten known ones (5-14), whose structures were elucidated using spectroscopic techniques. The isolate canophyllol (8) showed promising antibacterial activity against N. meningitides with MIC value of 31.25 μg/ml.

Matched MeSH terms: Antifungal Agents/isolation & purification*; Antifungal Agents/chemistry
Fulltext Onychomycosis: An Updated Review

Leung AKC, Lam JM, Leong KF, Hon KL, Barankin B, Leung AAM, et al.

Recent Pat Inflamm Allergy Drug Discov, 2020;14(1):32-45.
PMID: 31738146 DOI: 10.2174/1872213X13666191026090713

BACKGROUND: Onychomycosis is a common fungal infection of the nail.
OBJECTIVE: The study aimed to provide an update on the evaluation, diagnosis, and treatment of onychomycosis.
METHODS: A PubMed search was completed in Clinical Queries using the key term "onychomycosis". The search was conducted in May 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews published within the past 20 years. The search was restricted to English literature. Patents were searched using the key term "onychomycosis" in www.freepatentsonline.com.
RESULTS: Onychomycosis is a fungal infection of the nail unit. Approximately 90% of toenail and 75% of fingernail onychomycosis are caused by dermatophytes, notably Trichophyton mentagrophytes and Trichophyton rubrum. Clinical manifestations include discoloration of the nail, subungual hyperkeratosis, onycholysis, and onychauxis. The diagnosis can be confirmed by direct microscopic examination with a potassium hydroxide wet-mount preparation, histopathologic examination of the trimmed affected nail plate with a periodic-acid-Schiff stain, fungal culture, or polymerase chain reaction assays. Laboratory confirmation of onychomycosis before beginning a treatment regimen should be considered. Currently, oral terbinafine is the treatment of choice, followed by oral itraconazole. In general, topical monotherapy can be considered for mild to moderate onychomycosis and is a therapeutic option when oral antifungal agents are contraindicated or cannot be tolerated. Recent patents related to the management of onychomycosis are also discussed.
CONCLUSION: Oral antifungal therapies are effective, but significant adverse effects limit their use. Although topical antifungal therapies have minimal adverse events, they are less effective than oral antifungal therapies, due to poor nail penetration. Therefore, there is a need for exploring more effective and/or alternative treatment modalities for the treatment of onychomycosis which are safer and more effective.

Matched MeSH terms: Antifungal Agents/administration & dosage*; Antifungal Agents/adverse effects
Fulltext Effect of phenotypic switching on the biological properties and susceptibility to chlorhexidine in Candida krusei ATCC 14243

Arzmi MH, Abdul Razak F, Yusoff Musa M, Wan Harun WH

FEMS Yeast Res., 2012 May;12(3):351-8.
PMID: 22225549 DOI: 10.1111/j.1567-1364.2011.00786.x

Phenotypic switching is characterized as a virulence factor of Candida spp. This study was carried out to evaluate the phenotypic switching ability of C. krusei ATCC 14243 and to determine its effect on the biological properties, adherence capacity and susceptibility towards chlorhexidine digluconate (CHX). To induce switched generations C. krusei was cultured under nitrogen-depleted growth conditions by adding phloxine B. These phenotypically switched colonies were designated as the 1st generation. Subsequent sub-culturing was performed to produce the 2nd, 3rd and 4th switched generations. The recovery of the 3rd generation was the highest at 85.7% while that of the 4th generation was lower at 70.8%, and the recovery of the 1st and 2nd generations gradually reduced to 46.6% and 36.4%, respectively. All generations of C. krusei were susceptible towards CHX. The unswitched C. krusei was the most susceptible but the least adherent to coated hard surfaces. The 2nd generation was the least susceptible, but with the highest adherent ability. The minimum inhibition concentration and minimal fungicidal concentration of C. krusei of all generations were determined at 0.4 mg mL(-1) . These observations suggest that the switching activity of C. krusei induces changes to its biological properties and susceptibility towards CHX.

Matched MeSH terms: Antifungal Agents/pharmacology*

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