• Title/Summary/Keyword: Antifungal drugs

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Transcriptome sequencing revealed the inhibitory mechanism of ketoconazole on clinical Microsporum canis

  • Wang, Mingyang;Zhao, Yan;Cao, Lingfang;Luo, Silong;Ni, Binyan;Zhang, Yi;Chen, Zeliang
    • Journal of Veterinary Science
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    • v.22 no.1
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    • pp.4.1-4.13
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    • 2021
  • Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

Study on Distribution of Yeast Isolated from Clinical Specimens for Six Years in a University-affiliated Hospital (일개 대학병원의 임상검체에서 분리된 6년간의 효모균 분포에 관한 연구)

  • Ma, Pan-Gon;Kim, Sun-Joo;Seo, Choong-Won;Yu, Young-Bin;Kim, Young-Kwon
    • Journal of Digital Convergence
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    • v.13 no.9
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    • pp.369-375
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    • 2015
  • We investigated the prevalence of fungi isolated from a university-affiliated hospital during 6 years (2006-2011) to provide relevent information for the patient management. The general characteristics of the clinical isolates and gender, age, and type of specimens were analyzed. Among a total of 163,530 requested samples to culture for the Laboratory of Clinical Microbiology, Department of Laboratory Medicine, Gyeongsang National University Hospital in the Republic of Korea, 5,387 (3.3%) showd positive results for fungi. The most prevalent isolates were Candida albicans 41.9%, Candida glabrata 15.5%, and Candida tropicalis 14.6%. Total isolates of fungi increased from 526 in 2006 to 1,145 in 2011. They were most commonly isolated from sixties (27.0%) and seventies (26.5%). The most common clinical specimen was urine (44.8%). Males (52.4%) were slightly more than females (47.6%). In the future, a nationwide survey and additional antifungal convergence drugs susceptibility results will provide more useful information.

In vitro antimicrobial activity of aqueous and ethanol extracts of Euphorbia hirta

  • Reezal, I.;Somchit, MN;Nur, I. Elysha;Hasmawie, R.;Chong, PP;Mutalib, AR;Ahmad, Z.
    • Advances in Traditional Medicine
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    • v.3 no.4
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    • pp.191-195
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    • 2003
  • Euphorbia hirta, locally called 'ara tanah' or 'susun nabi' in Malaysia is a small annual herb common to the tropical countries and belongs to the same family as the tic and tapioca. E. hirta has had a long history of usage in the treatment of various ailments. In this current study, in vitro sensitivity test of crude aqueous and ethanol extracts of leaves and barks of E. hirta was carried out against bacteria (Escherichia coli, Salmonella enteritidis, Staphylocccus aureus and Bacillus subtilis) and fungi (Microsporum canis, Aspergillus fumigatus, Candida albicans and Candida tropicalis) using the discs diffusion method. The extract-impregnated discs (20, 40 and $80\;{\mu}g/{\mu}l$), the E. hirta extracts inhibited the growth of all the bacteria tested. The growth of C. albicans was inhibited in a concentration dependent manner by the aqueous leaves and barks extracts. C. tropicalis was found to be sensitive to the aqueous leaves extracts. The results were compared to antibacterial drugs of chloramphenicol, ampicilin, penicillin G, and enrofloxacine; and to antifungal drug of ketoconazole, itraconazole and miconazole. In this current study, it can be concluded that this plant has antimicrobial activity that is as potent as the standard antimicrobial drugs against certain microorganisms.

Antifungal Activity of Non-thermal Dielectric Barrier Discharge Plasma Against Clinical Isolates of Dermatophytes

  • Ali, Anser;Hong, Young June;Lee, SeungHyun;Choi, Eun Ha;Park, Bong Joo
    • Proceedings of the Korean Vacuum Society Conference
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    • 2014.02a
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    • pp.260-260
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    • 2014
  • Dermatophytes can invade in keratinized tissues and cause dermatophytosis [1] that rank among the most widespread and common infectious diseases world-wide. Although several systemically and topically administered drugs with activities against these fungi are available, still complete eradication of some of these infections, is difficult and relapses and remissions are often observed [2,3]. In addition, some people are allergic to many of the available drugs which add complications even more. Therefore, the search for novel, selective and more effective therapy is always required and it may help the clinicians to choose the correct treatment for their patients. Non-thermal plasmas primarily generate reactive species and recently have emerged as an efficient tool for medical applications including sterilization. In this study, we evaluated the ability of non-thermal dielectric barrier discharge (DBD) plasma for the inactivation of clinical isolates of Trichophyton genera, Trichophyton mentagrophytes (T. mentagrophytes) and Trichophyton rubrum (T. rubrum), which cause infections of nails and skin and, are two of the most frequently isolated dermatophytes [4]. Our results showed that DBD plasma has considerable time dependent inactivation potential on both T. mentagrophytes and T. rubrum in-vitro. Furthermore, the mechanisms for plasma based T. mentagrophytes and T. rubrum inactivation and planning for in-vivo future studies will be discussed.

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Antifungal susceptibility of Candida spp isolated from bovine mammary glands and teat cups of milking machines (Candida속 균의 항진균성약제에 대한 감수성)

  • Yeo, Sang-geon;Chung, Kyu-young;Cho, Hee-tack
    • Korean Journal of Veterinary Research
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    • v.29 no.1
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    • pp.69-73
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    • 1989
  • In vitro antifungal susceptibility test was carried out on 53 strains of Candida spp isolated from milk of dairy cows with subclinical mastitis and teat cups of milking machines, Nystatin, clotrimazole, miconazole, econazole, 5-fluorocytosine, cycloheximide, haloprogin and griseofulvin were tested by the agar dilution method. The 84.8% to 98.2% of Candida strains were inhibited by clotrimazole, econazole and miconazole at $${\leq_-}25{\mu}g/ml$$, and clotrimazole was most active. Interspecies differences of antifungal susceptibility were recognized and these were as follows. C albicans was most sensitive to clotrimazole (GM-MIC, $5.49{\mu}g/ml$) followed by 5-fluorocytosine, econazole and miconazole. C pseudotropicalis and C guilliermondii were notably sensitive to haloprogin, clotrimazole, miconazole, cconazole, 5-fluorocytosine, and haloprogin (GM-MIC, $0.17{\sim}0.19{\mu}g/ml$) was most active. C krusei was most sensitive to cycloheximide (GM-MIC, $0.54{\mu}g/ml$) followed by clotrimazole, haloprogin, miconazole and econazole. C parapsilosis was somewhat sensitive to econazole, cycloheximide, clotrimazole, and econazole (GM-MIC, $7.26{\mu}g/ml$) was most active. C tropicalis showed very low sensitivity to all tested drugs (GM-MIC, $${\geq_-}20.32{\mu}g/ml$$).

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Activity of Allyl Isothiocyanate and Its Synergy with Fluconazole against Candida albicans Biofilms

  • Raut, Jayant Shankar;Bansode, Bhagyashree Shridhar;Jadhav, Ashwini Khanderao;Karuppayil, Sankunny Mohan
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.685-693
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    • 2017
  • Candidiasis involving the biofilms of Candida albicans is a threat to immunocompromised patients. Candida biofilms are intrinsically resistant to the antifungal drugs and hence novel treatment strategies are desired. The study intended to evaluate the anti-Candida activity of allyl isothiocyanate (AITC) alone and with fluconazole (FLC), particularly against the biofilms. Results revealed the concentration-dependent activity of AITC against the planktonic growth and virulence factors of C. albicans. Significant (p <0.05) inhibition of the biofilms was evident at ${\leq}1mg/ml$ concentrations of AITC. Notably, a combination of 0.004 mg/ml of FLC and 0.125 mg/ml of AITC prevented the biofilm formation. Similarly, the preformed biofilms were significantly (p <0.05) inhibited by the AITC-FLC combination. The fractional inhibitory concentration indices ranging from 0.132 to 0.312 indicated the synergistic activity of AITC and FLC against the biofilm formation and the preformed biofilms. No hemolytic activity at the biofilm inhibitory concentrations of AITC and the AITC-FLC combination suggested the absence of cytotoxic effects. The recognizable synergy between AITC and FLC offers a potential therapeutic strategy against biofilm-associated Candida infections.

Surgical Treatment of Pleural Aspergillosis a case report (Pleural Aspergillosis 치험 1례)

  • Yang, Hyeon-Ung;Choe, Jong-Beom;Choe, Sun-Ho
    • Journal of Chest Surgery
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    • v.30 no.5
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    • pp.544-547
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    • 1997
  • We have experienced a case of pleural aspergillosis. A 50 year old female complained of malaise, anorexia, coughing with sputum, and right sided pleuritic chest pain of two weeks' duration. About ten years ago, she had been treated for pulmonary tuberculosis with medication. Chest radiography showed right pyopneumothorax with cavitation in the rig t upper lung and Chest computed topography revealed right loculated pyopneumothorax with cavity formation suggesting bronchopleural fistula. Decortication and wedge resection with pleurectomy were performed. The postoperative course was satisfactory and has been in good condition up to now. Pleural aspergillosis is a very rare and potentially life-threatening disease, but we have had good results without significant complications by treatment with systemic antifungal drugs and surgical operation.

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Combination Strategy to Increase Cyclosporin A Productivity by Tolypocladium niveum Using Random Mutagenesis and Protoplast Transformation

  • Lee, Mi-Jin;Duong, Cae Thi Phung;Han, Kyu-Boem;Kim, Eung-Soo
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.869-872
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    • 2009
  • The cyclic undecapeptide cyclosporin A (CyA), one of the most valuable immunosuppressive drugs, is produced nonribosomally by a multifunctional cyclosporin synthetase enzyme complex by the filamentous fungus Tolypocladium niveum. To increase CyA productivity by wild-type T. niveum (ATCC 34921), random mutagenesis was first performed using an antifungal agar-plug colony assay (APCA) selection approach. This generated a mutant strain producing more than 9-fold greater CyA than the wild-type strain. Additionally, a foreign bacterial gene, Vitreoscilla hemoglobin gene (VHb), was transformed via protoplast regeneration and its transcription was confirmed by RT-PCR in the UV-irradiated mutant cell. This led to an additional 33.5% increase of CyA production. Although most protoplast-regenerated T. niveum transformants tend to lose CyA productivity, the optimized combination of random mutagenesis and protoplast transformation described here should be an efficient strategy to generate a commercially valuable, yet metabolite low-producing, fungal species, such as CyA-producing T. niveum.

INVASIVE ASPERGILLOSIS OF THE MAXILLARY ANTRUM AND LUNG IN A PATIENT WITH DIABETES MELLITUS AND LIVER CIRRHOSIS (당뇨 및 간경변 환자의 상악동과 폐에서 발생한 침윤성 국균증의 치험례)

  • Kim, Ill-Kyu;Lee, Seong-Jun;Ha, Soo-Yong;Chu, Young-Chae;Shin, Yong-Woon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.13 no.4
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    • pp.456-461
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    • 1991
  • This is a case report of invasive aspergillosis of the right maxillary antrum and the left lung in a 43 year-old male patient with diabetes mellitus and liver cirrhosis. The results were as follows. 1. Invasive aspergilliosis should be considered in compromised patients who have nasal symptomatology, infraorbital swelling and pain. 2. Invasive aspergillosis is a rapidly progressive mycotic infection of the sinus which may extend to the orbit, nasal cavity and cheek. 3. Surgical intervention is particularly urgent in orbital aspergillosis in patient in whom the eyesight is still preserved. 4. Diagnosis depends upon pathological demonstration of tissue invasion by organism with the typical morphology of aspergillus species. 5. Long-term antifungal drugs should be administrated postoperatively in pathint with invasive aspergillosis.

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The Stress-Activated Signaling (SAS) Pathways of a Human Fungal Pathogen, Cryptococcus neoformans

  • Jung, Kwang-Woo;Bahn, Yong-Sun
    • Mycobiology
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    • v.37 no.3
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    • pp.161-170
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    • 2009
  • Cryptococcus neoformans is a basidiomycete human fungal pathogen that causes meningoencephalitis in both immunocompromised and immunocompetent individuals. The ability to sense and respond to diverse extracellular signals is essential for the pathogen to infect and cause disease in the host. Four major stress-activated signaling (SAS) pathways have been characterized in C. neoformans, including the HOG (high osmolarity glycerol response), PKC/Mpk1 MAPK (mitogen-activated protein kinase), calcium-dependent calcineurin, and RAS signaling pathways. The HOG pathway in C. neoformans not only controls responses to diverse environmental stresses, including osmotic shock, UV irradiation, oxidative stress, heavy metal stress, antifungal drugs, toxic metabolites, and high temperature, but also regulates ergosterol biosynthesis. The PKC(protein kinase C)/Mpk1 pathway in C. neoformans is involved in a variety of stress responses, including osmotic, oxidative, and nitrosative stresses and breaches of cell wall integrity. The $Ca^{2+}$/calmodulin- and Ras-signaling pathways also play critical roles in adaptation to certain environmental stresses, such as high temperature and sexual differentiation. Perturbation of the SAS pathways not only impairs the ability of C. neoformans to resist a variety of environmental stresses during host infection, but also affects production of virulence factors, such as capsule and melanin. A drug(s) capable of targeting signaling components of the SAS pathway will be effective for treatment of cryptococcosis.