• Journal of Microbiology and Biotechnology
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• v.29 no.1
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• pp.171-177
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• 2019

Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p < 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.

• Journal of Microbiology and Biotechnology
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• v.32 no.7
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• pp.911-917
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• 2022

As valuable antibiotics, microbial natural products have been in use for decades in various fields. Among them are polyene compounds including nystatin, amphotericin, and nystatin-like Pseudonocardia polyenes (NPPs). Polyene macrolides are known to possess various biological effects, such as antifungal and antiviral activities. NPP A1, which is produced by Pseudonocardia autotrophica, contains a unique disaccharide moiety in the tetraene macrolide backbone. NPP B1, with a heptane structure and improved antifungal activity, was then developed via genetic manipulation of the NPP A1 biosynthetic gene cluster (BGC). Here, we generated a Streptomyces artificial chromosomal DNA library to isolate a large-sized NPP B1 BGC. The NPP B1 BGC was successfully isolated from P. autotrophica chromosome through the construction and screening of a bacterial artificial chromosome (BAC) library, even though the isolated 140-kb BAC clone (named pNPPB1s) lacked approximately 8 kb of the right-end portion of the NPP B1 BGC. The additional introduction of the pNPPB1s as well as co-expression of the 32-kb portion including the missing 8 kb led to a 7.3-fold increase in the production level of NPP B1 in P. autotrophica. The qRT-PCR confirmed that the transcription level of NPP B1 BGC was significantly increased in the P. autotrophica strain containing two copies of the NPP B1 BGCs. Interestingly, the NPP B1 exhibited a previously unidentified SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) inhibition activity in vitro. These results suggest that the Streptomyces BAC cloning of a large-sized, natural product BGC is a valuable approach for titer improvement and biological activity screening of natural products in actinomycetes.

• The Journal of Korean Academy of Prosthodontics
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• v.32 no.2
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• pp.268-280
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• 1994

Tissue conditioners have been used for treatment of denture stomatitis caused by wearing of dentures. Early studies pointed out Candide albicans (C. albicans) as main etiologic factor, and antifugal agents were added for control of the species. But there is a little information about broad comparison on the effect of tissue conditioners and antifungal agents added. The purpose of the present study was to compare the inhibiting effect of four tissue conditioners and one temporary soft liner on the growth of C. albicans for treatment of denture stomatitis using gel diffusion method by measuring diameter of the zone of growth inhibition. Three antifungal agents were added to each material for evaluation of the effect of added agents. Finally, observation was made to evaluate the effect of the loss of antifungal elements by aging of the specimen. The results of this study were obtained as follows : 1. Tempo had remarkable antifungal effect showing the zone of growth inhibition as 2.35 mm at 1st day, and was most effective on End: 4th and 7th day from incubation (p<0.05). But Coecomfort, Dura conditioner, Visco-gel, Coe-soft had little antifungal effect from the 1st day of incubation. 2. Nystatin was most effective showing 9.60-12.04 mm of zone of inhibition at the 1st day from incubation. The antifungal properties were reduced to amphotericin B, chlorhexidine and materials without agent (p<0.05), and the effect was diminished by time. 3. As pretreatment with amphotericin B, nystatin, chlorhexidine, Tempo was very effective at the 1st day from incubation showing zone of inhibition as 3.65, 12.04, 4.78 mm with addition of each agent. Dura conditioner had strongest antifungal effect at the next day as 2.86, 5.33, 1.29 mm of zone of inhibition, and yielding results of Coe-comfort, Tempo, Coe-soft was shown at 4th and 7th day from incubation (p<0.05). Taken all together, tissue conditioners have little antifungal effect except Tempo. Formation of the zone of growth inhibition was due to agents amphotericin B, nystatin, chlorhexidine and nystatin was most effective. Conclusively, it is advisable to select material which is effective on the growth of C. albican and consider addition of antifungal agents for treatment of denture stomatitis.

• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.1-6
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• 2001

The aim of this study was to determine optimal therapeutic dose of antifungal agents for dermatophytes. Forty nine dermatophytes were isolated form dogs and cats showing skin lesions and were tested for their in vitro susceptibility to nystatin, griseofulvin, terbinafine, ketoconazole and fluconazole by broth microdilution test. Terbinafine showed the lowest MIC value among the antifungal agents tested, and MIC values ranged from 0.002 to 0.016 $\mu\textrm{g}$/ml. Fluconazole showed the highest MIC values among the antifungal agents tested, and MIC values ranged from 32 to 512 $\mu\textrm{g}$/ml. MIC values of nystatin, griseofulvin and ketoconazole ranged from 1.12 to 4.48 $\mu\textrm{g}$/ml, 0.5 to 4.0 $\mu\textrm{g}$/ml, and 1.6 to 12.8 $\mu\textrm{g}$/ml, resistant to griseofulvin, and that antifungal susceptibility test was needed to determine optimal therapeutic dose of antifungal agents for each dermatophyte.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.163-163
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• 1993

대상환자는 모두 23명이였으여, 이중 12명은 fluconazole을, 11명은 nystatin을 투여받았다. 두 군사이에 연령, 남여비, 기저질환, 진균감염의 위험요소는 차이가 없었다. 투약기간은 fluconazole군(F)이 24일, nystatin군(N)이 23일이였다. 중도탈락은 3례로 F중 MRSA ？혈증 1례, N중 오심, 구토 1례외 Stevens-Johnson증후군 1례였다. 평가가능한 20례중, F 11례중 8례와, N 9례중 4례에서 진균감염중의 예방에 성공하였고, F 3례와 N 5례는 실패하였다. 실패한 F 3례는 코의 피부조직에서 aspergillus가 중명된 1례와 경험적으로 amphotericin을 투여한 2례였고, N 5례는 혈액배양에서 Candida tropicalis가 분리된 1례와 경험적 amphotericin을 받은 4례였다. 진균의 colonization은 F중 3균주는 치료중 소실되었으나, 2례는 증가하였다. N은 1균주가 소실된 반면, 3례는 증가하였다. Colonization이 증가한 F 2례는 C. albicans와 Trichosporon beigelli가 대변에서 분리된 경우이고. M 3례는 대변에서 C. albicans가 분리된 1례, 구강에서 aspergillus가 분리된 1례, 혈액배양에서 C. tropicalis가 분해된 1례였다. 부작용은 오심 구토가 F중 1례, N중 2례 였으며, 이중 N의 1례는 증상이 심하여 투약을 중지하였다. 간기능 검사상 SGOT/SGPT의 상승은 F 12중 3례, N 11중 2례에서 관찰되었으나, 두 군사이에 통계학적으로 유의한 차이는 없었다.

• Korean Journal of Microbiology
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• v.23 no.4
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• pp.309-314
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• 1985

Autoxotrophic mutants of a cellulolytic baterium Cellulomonas sp. CS 1-1 were grown at $30^{\circ}C$ for 6hr using a complete medium containing 0.5M sucrose and for another 90 min after addition of 0.3 U/ml penicillin G, and were protoplasted by 0.2mg/ml lysozyme for 2hr. Prototrophic recombinants were obtained at the rates of $10^{-3}$ to $10^{-5}$by fusing the protoplasts in the presence of 40% polyethyleneglycol3350. Nystatin could be used to eliminate fungal contamination during the regeneration of the plotaplasts.

• Journal of Ginseng Research
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• v.10 no.1
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• pp.66-75
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• 1986

Influnces of Fuiarium solani and Phytophthora cactorum infection on the changes in saponin components of Korean ginseng (Panax ginseng C.A. Meyer)roots and some of the biology of those fungi in relation to ginseng root were investigated. Mycelial growth of F. solani was decreased as increasing concentration of the water extracts of fresh ginseng roots, while that of P. cactorum was increased as increasing the concentration of the water extracts and crude saponin. Mycelial growth of F. solani, however, was increased as increasing concentration of crude ginseng saponin upto 20 ppm, while it was tended to be decreased when the concentration was higher than 50 ppm. Nystatin also suppresed the growth of F. solani as increasing its concentration, but it did not affected on the growth of p. cactorum. Ginsenoside Ra and Ro components were not detected in ginseng roots inoculated with F. solani or P. cactorum. Panaxadiol gisenosides were increased by 3.0%, whereas panaxatriol ginsenosides were decreased by 34.9% in ginseng roots inoculated with F. iolani. In ginseng roots inoculated with P. cactorum panaxadiol ginsenosides were increased by 21.1%, but panaxatriol ginsenosides were decreased by 23.5%. PD/PT ratio in ginseng roots inoculated with F. solani or P. cactorum were equally increased by 58.4% in spite of differences in the change of panaxadiol and panaxatriol ginsenosides. The total saponin components of ginseng roots inoculated with F. solani or P. cactorum were decreased by 17.8% and 2.5%, respectively.

• The Journal of the Korean dental association
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• v.48 no.5
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• pp.355-364
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• 2010

The frequency of mucosal and cutaneous fungal infection is increasing worldwide, which is due to the increase of immunocompromised patients. Candida albicans are the principal species associated with human oral mycosis and are known to be the most virulent among pathogenic Candida spp. In this review, oral candidiasis were classified and oral mucosal manifestations of candidiasis were filed. And its diagnosis and management would be reviewed briefly.

• Korean Journal of Microbiology
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• v.40 no.3
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• pp.221-225
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• 2004

Novel cytochrome P450 hydroxylase (CYP) genes were isolated and characterized from P. autotrophica cosmid DNA library using an actinomycete CYP-specific PCR product as a screening probe. The cosmids containing four unique CYP genes (pESK601, 602, 603, 604, 605) were identified, and the four CYP genes were completely sequenced to be homologous to other known Actinomycetes CYP genes involved in various secondary metabolic pathways. Among all novel actinomycete CYP genes found in P. autotrophica, the CYP genes present in pESK601 were revealed to be highly homologous to the CYP genes involved in polyene-type amphotericin and nystatin antibiotic biosynthesis. The nucleotide sequences of the CYP flanking region in pESK601 also revealed the polyene-type biosynthetic genes, implying the presence of a cryptic polyene-type antifungal biosynthetic gene cluster in P. autotrophica.

• Korean Journal of Pharmacognosy
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• v.23 no.4
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• pp.240-247
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• 1992

Impatiens balsamina Linne(Balsaminaceae) known as 'BONG SUN HWA' in Korea and has been used for the treatment of scrofulosis, carbunculus and dysenteria etc. Bioassay-guided fractionation of MeOH extract from the whole plants of Impatiens balsamina has afforded a simple naphthoquinone derivative, 2-methoxy-1,4-naphthoquinone. The structure of this compound was established by spectroscopic methods. This compound possessed strong antifungal activity against Candida albicans, AspergiIlus niger, Crytococcus neoformans and Epidermophyton floccusum. The activity of 2-methoxy-1,4-naphthoquinone on E. floccusum $(MIC{\;}:{\;}5.0{\;}{\mu}g/ml)$ was the same potency as that of nystatin. It showed also strong antibacterial activity against gram-positive bacteria Bacillus subtilis as well as gram-negative bacteria Salmonella typhimurium. Although the activity of this compound on gram-negative bacteria was lower than that of gram-positive bacteria.