• Microbiology and Biotechnology Letters
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• v.51 no.4
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• pp.500-506
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• 2023

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is emerging as a worldwide public health threat. Recently, Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing sequence type (ST) 307 was identified main clone of CRKP, and dissemination of ST307 was reported in South Korea. This study examined the molecular characteristic and antimicrobial resistance pattern of 50 CRKP isolated from a tertiary hospital in Daejeon, from March 2020 to December 2021. Epidemiological relationship was analyzed by Multilocus sequence typing (MLST) and antimicrobial susceptibility test was determined using disk-diffusion method. PCR and DNA sequence analysis were performed to identify carbapenemase genes. CRKP infections were significantly more frequent in males and the patients aged ≥ 60 years. Among the 50 CRKP isolates, 46 isolates (92.0%) were multidrug-resistant (MDR), and 44 isolates (88.0%) were carbapenemase-producing K. pneumoniae (CPKP). The major carbapenemase type was KPC-2 (36 isolates, 72.0%) and New Delhi metalloenzyme-1 (NDM-1) and NDM-5 were identified in 7 isolates (14.0%) and 1 isolate (2.0%), respectively. In particular, 88.9% (32/36) of KPC-2-producing K. pneumoniae belonged to ST307, whereas 87.5% (7/8) of NDM-1,-5-producing K. pneumoniae belonged to non-ST307. These results suggest that proper infection control and effective surveillance network need to prevent not olny the spread of ST307, but also the development of non-ST307.

• Journal of Microbiology
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• v.42 no.1
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• pp.14-19
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• 2004

Salmonella enterica serovar Typhimurium DT104 (Salmonella Typhimurium DT104 or DT104) has been emerging as a common pathogen for human in Korea since 1997. In order to compare the genomic relationship and to search for the dominant strains in Korea, we conducted pulsed-field gel electrophoresis (PFGE) and IS200 fingerprinting of 25 epidemiological unrelated isolates from human and animals from Korea and cattle from America. Two Salmonella Typhimurium DT104 isolates from human in Korea and all 8 isolates from American cattle had indistinguishable patterns from the PFGE and IS200 fingerprinting but multidrug-resistant Salmonella Typhimurium isolates, including DT104, from Korean animals had diverse genetic patterns. The data suggest that a dominant DT104 strain might have circulated between Korean and American cattle and that it had a high level of clonality.

• Clinical and Experimental Pediatrics
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• v.51 no.10
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• pp.1042-1046
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• 2008

The fluoroquinolones are an important group of antibiotics widely used in the treatment of various infectious diseases in adults, as a result of an excellent spectrum of activity, good tissue penetration and convenient ways of administration. In recent decades, there has been extensive development, clinical investigation, licensure and use of fluoroquinolone antibiotics. However, the use of fluoroquinolones in children has been limited because of their potential to induce arthropathy in juvenile animals. Despite class label warnings against use in children, prescriptions for quinolone antibiotics to treat infections in children have become increasingly prevalent. The main use of fluoroquinolones in pediatrics should be, understandably, in serious life-threatening infections for which other antibiotics therapies are not effective or available. While most of the published studies failed to detect an increased rate of articular adverse effects in children treated with fluoroquinolones, an increase in the use of these compounds, particularly in community-acquired lower respiratory infections, could accelerate the emergence of multidrug-resistant (including fluoroquinolone) pneumococcal strains. This review will discus the main issues related to the use of fluoroquinolones in children, the major problems of resistance developing among these compounds, with special emphasis on the potential side effects and skilled use of these alternative potent drugs in pediatric infection.

• Microbiology and Biotechnology Letters
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• v.47 no.4
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• pp.651-661
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• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1426-1432
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• 2018

Staphylococcus aureus causes a broad variety of diseases. The spread of multidrug-resistant S. aureus highlights the need to develop new ways to combat S. aureus infections. Sortase A (SrtA) can anchor proteins containing LPXTG binding motifs to the bacteria surface and plays a key role in S. aureus infections, making it a promising antivirulence target. In the present study, we used a SrtA activity inhibition assay to discover that isovitexin, a Chinese herbal product, can inhibit SrtA activity with an $IC_{50}$ of $28.98{\mu}g/ml$. Using a fibrinogen-binding assay and a biofilm formation assay, we indirectly proved the SrtA inhibitory activity of isovitexin. Additionally, isovitexin treatment decreased the amount of staphylococcal protein A (SpA) on the surface of the cells. These data suggest that isovitexin has the potential to be an anti-infective drug against S. aureus via the inhibition of sortase activity.

• Journal of Microbiology and Biotechnology
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• v.28 no.11
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• pp.1771-1781
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• 2018

The emergence of multidrug-resistant microorganisms, as well as fungal infectious diseases that further threaten health, especially in immunodeficient populations, is a major global problem. The development of new antifungal agents in clinical trials is inferior to the incidence of drug resistance, and the available antifungal agents are restricted. Their mechanisms aim at certain characteristics of the fungus in order to avoid biological similarities with the host. Synthesis of the cell wall and ergosterol are mainly targeted in clinical use. The need for new approaches to antifungal therapeutic agents or development alternatives has increased. This review explores new perspectives on mechanisms to effectively combat fungal infections and effective antifungal activity. The clinical drug have a common feature that ultimately causes caspase-dependent cell death. The drugs-induced cell death pathway is associated with mitochondrial dysfunction, including mitochondrial membrane depolarization and cytochrome c release. This mechanism of action also reveals antimicrobial peptides, the primary effector molecules of innate systems, to highlight new alternatives. Furthermore, drug combination therapy is suggested as another strategy to combat fungal infection. The proposal for a new approach to antifungal agents is not only important from a basic scientific point of view, but will also assist in the selection of molecules for combination therapy.

• Bulletin of the Korean Chemical Society
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• v.32 no.9
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• pp.3219-3222
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• 2011

Three types of ${\beta}$-ketoacyl acyl carrier protein synthase (KAS) are important for overcoming the bacterial resistance problem. Recently, we reported the discovery of a antimicrobial flavonoid, YKAF01 (3,6-dihydroxyflavone), which exhibits antibacterial activity against Gram-positive bacteria through inhibition of ${\beta}$-ketoacyl acyl carrier protein synthase III (KAS III). In this report, we suggested that YKAF01 can be an inhibitor ${\beta}$-ketoacyl acyl carrier protein synthase I (KAS I) with dual inhibitory activity for KAS I as well as KAS III. KAS I is related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. We performed docking study of Escherichia coli KAS I (ecKAS I) and YKAF01, and determined their binding model. YKAF01 binds to KAS I with high binding affinity ($2.12{\times}10^6$) and exhibited an antimicrobial activity against the multidrug-resistant E. coli with minimal inhibitory concentration (MIC) value of 512 ${\mu}g$/mL. Further optimization of this compound will be carried out to improve its antimicrobial activity and membrane permeability against bacterial cell membrane.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1639-1642
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• 2014

The multidrug resistance phenotype is one of the major problems in development of cancer cell resistance to chemotherapy. Some natural compounds from medicinal plants have demonstrated promising capacity in enhancing anticancer effects in drug resistant cancer cells. We aimed to investigate whether mangiferin might have an ability to re-sensitize MCF-7 breast cancer cells previously treated with short-term doxorubicin in vitro, through the modulation of efflux transporters, P-glycoprotein (P-gp), MRP1 and BCRP. We exposed MCF-7 breast cancer cells pretreated with doxorubicin for 10 days to mangiferin (10, 25 or 50 ${\mu}M$) for 96 hours. Afterwards, we evaluated influence on cell viability and level of mRNA expression of P-gp, MRP1 and BCRP. Doxorubicin given in combination with mangiferin at low concentrations (10 and 25 ${\mu}M$) failed to give significant reduction in cell viability, while at the highest concentrations, the combination significantly reduced cell viability. The mRNA expression analysis of P-gp, MRP1 and BCRP showed that mangiferin had inhibitory effects on P-gp but no effects on MRP1 and BCRP. In conclusion, we suggest that mangiferin at high concentrations can be used as chemosensitizer for doxorubicin therapy. This effect might be attributed by inhibitory effects of mangiferin on P-glycoprotein expression.

• Journal of Chest Surgery
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• v.34 no.1
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• pp.72-79
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• 2001

배경: 일반적으로 다제내성 폐결핵의 경우 화학요법만으로는 치료성적이 만족스럽지 못하였다. 이에 수술적 치료와 항결핵 화학요법의 병합사용이 높은 균음전율과 장기 생존율을 보여주고 있으므로 이러한 치료전략이 다제내성 폐결핵환자의 일반적인 치료방법으로 정립되리라는 전망을 갖게 하고 있다. 대상 및 방법: 1995년 1월부터 1999년 12월까지 국립마산결핵병원에서 폐결핵에 대한 수술을 시행받은 130례 중 다제내성 폐결핵으로 폐절제수술을 받은 49례를 대상으로 의무기록 및 검사기록 등을 근거로 후향적 조사를 실시하였다. 결과: 대상환자들의 평균연령은 35세였고, 내성약제의 수는 평균 4.5였다. 43례(87.8%)의 환자에서 공동성 병소를 보였으며 31례(63.3%)의 환자에서 술전 객담내 균양성 소견을 보였다. 수술술식은 12례에서 전폐적출술을, 28례에서 폐엽절제술을, 7례에서는 폐엽절제술과 구역절제술 혹은 설상절제술 등을, 그리고 설상절제술과 공동성형술을 각각 1례에서 시행하였다. 술후 지속적인 내과적 약물치료를 병합하여 장기적인 균음전율은 93.5%였고 술후 사망환자는 없었다. 술후 합병증으로는 1주일 이상 지속되는 공기유출 6례와 술후 출혈, 창상분열이 각각 1례씩 있었다. 결론: 다제내성 폐결핵환자에서 폐절제 수술에 대해서는 적절한 적응증, 수술후 처방, 그리고 술후 치료기간 등에 대한 이견이 있지만 적극적으로 고려되어야 하며 술후 내과적 치료와 병행함으로 좋은 치료효과를 얻을 수 있었다.

• Clinical and Experimental Pediatrics
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• v.56 no.5
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• pp.196-201
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• 2013

Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.