• Genomics & Informatics
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• 제21권3호
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• pp.42.1-42.23
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• 2023

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

• 생명과학회지
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• 제24권3호
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• pp.266-273
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• 2014

본 연구에서는 국내 시판 중인 정유의 화학적 구성, 항균 및 항산화 효과를 조사하였다. 정유의 성분 분석은 GC-MS법을 이용하였다. 정유는 그람음성, 양성 및 다약제 내성균에 대하여 광범위한 항균 범위를 보여주었다. 정유 5종의 항균활성은 40개 병원성 세균에 대한 MIC로 측정하였다. Lemongrass와 manuka는 0.0625-0.5% (v/w), tea tree는 0.03125-1.0% (v/w), thyme 0.0625-1.0% (v/w) 및 ravensara는 1-4% (v/w)의 MIC 수치를 나타내었다. 정유의 항산화 활성은 환원력 및 DPPH법으로 평가하였다. 5종의 정유 모두 농도 의존적으로 DPPH free radical 저해 및 환원력을 가지고 있었으며, thyme이 대조군인 ascorbic acid와 비교 시 가장 높은 항 산화능을 보였다. 5종의 정유 모두 고른 항균 및 항산화능을 가지고 있으며, 이중 thyme이 가장 높은 항균활성 및 항산화능을 가지고 있어 천연 항균 항산화제로써의 가치가 있다고 생각되었다. 본 연구진은 국내 시판중인 정유 5종의 성분분석, 항균 및 항산화 활성을 처음으로 비교 분석하여 보고하였다.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.691-696
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• 2007

Purpose: The emergency of multi-drug resistant stains of bacteria represents a challenge in the field of plastic surgery. Especially, MRSA(methycillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa have strong pathogenicity as well as multi-drug resistance so that they have become a lot more problematic strains. This study has been planned to reduce the bacterial burden by applying $Acticoat^{(R)}$(Smith & Nephew Healthcare, Hull, England)dressing into the chronic wounds infected by multi-drug resistant strains and to facilitate their healing. Methods: Nanocrystalline silver dressings($Acticoat^{(R)}$) were applied to chronic wound infected by MRSA or Pseudomonas aeruginosa. Multi-drug resistant bacteria were smeared over a slide glass using sterilized cotton swabs and gram stains were performed directly before and after applying $Acticoat^{(R)}$ dressings at 1, 24, 48 and 72 hours. The gram-stained slides were observed using an optical microscope magnified 1000 times(${\times}1000$). The bacterial counts of the control group(0 hour) were compared to those of the experimental groups(1, 24, 48, and 72 hour). Paired T-test was used to assess a statistical significance. MRSA was cultured in two BAPs(blood agar plate) and two MacConkey plates with streak plate method. None were interventions on one culture plate, while on the other culture plate, $Acticoat^{(R)}$ was placed in a square shape and cultured for 72 hours at $37^{\circ}C$, then plates were examined. Pseudomonas aeruginosa was cultured in the same manner as MRSA. Results: There are the large amount of declination of bacterial counts with statistical significance after $Acticoat^{(R)}$ dressing. The bacteria grew in culture plate without specific intervention, but no bacteria grew in culture plate with applying of $Acticoat^{(R)}$ dressing. Conclusion: We believe that $Acticoat^{(R)}$ dressing could be used as an effective method of treating chronic wounds which are infected by multi-drug resistant organisms.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3309-3315
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• 2016

Helicobacter pylori as the second most common cause of gastric cancer in the world infects approximately half of the developed countries population and 80% of the population living in developing countries. Integrons as genetic reservoirs play major roles in dissemination of antimicrobial resistance genes. To the best of our knowledge, this is the first study to report carriage of class 1 and 2 integrons and associated gene cassettes in H. pylori isolates from Iran. This cross-sectional study was conducted in Tehran among 110 patients with H. pylori infection. Antimicrobial susceptibility testing (AST) for H. pylori strains were assessed by the micro broth dilution method. Class 1 and 2 integrons were detected using PCR. In order to determine gene cassettes, amplified fragments were subjected to DNA sequencing of both amplicon strands. The prevalence of resistance to clarithromycin, metronidazole, clarithromycin, tetracycline, amoxicillin, rifampin, and levofloxacin were 68.2% (n=75), 25.5% (n=28), 24.5% (n=27), 19.1% (n=21), 18.2% (n=20) and 16.4% (n=18), respectively. Frequency of multidrug resistance among H. pylori isolates was 12.7%. Class 2 integron was detected in 50 (45.5%) and class 1 integron in 10 (9.1%) H. pylori isolates. The most predominant gene cassette arrays in class 2 integron-bearing H. pylori were included sat-era-aadA1, dfrA1-sat2-aadA1, blaoxa2 and, aadB whereas common gene cassette arrays in class 1 integron were aadB-aadA1-cmlA6, aacA4, blaoxa2, and catB3. The high frequency of class 2 integron and multidrug resistance in the present study should be considered as a warning for clinicians that continuous surveillance is necessary to prevent the further spread of resistant isolates.

• Natural Product Sciences
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• 제13권3호
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• pp.251-254
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• 2007

Dioxopiperazine alkaloids, 12R,13S-dihydroxyfumitremorgin C (1), fumitremorgin C (2), and brevianamide F (3), were isolated from the marine-derived fungus Pseudallescheria, and the absolute stereostructures of compounds 1 - 3 were elucidated on the basis of chemical and physicochemical evidence. Compounds 1 - 3 showed an antibacterial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and multidrug-resistant S. aureus. The MIC (minimum inhibitory concentration) values of compounds 1 - 3 were 125 ${\mu}g/mL$ for all strains.

• 대한임상검사과학회지
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• 제48권2호
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• pp.94-101
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• 2016

Acinetobacter species는 중요한 기회감염균으로 빈번하게 원내감염을 일으킨다. 뿐만 아니라 다제내성을 보이는 경우가 많아 치료를 위한 항균제 선택이 매우 제한적이다. 본 연구에서는 Acinetobacter species 68균주를 대상으로 하여 다양한 carbapenemase 유전자를 조사했다. 디스크확산법으로 항균제 감수성 양상을 조사했으며 다중 중합효소연쇄반응을 통해 carbapenemase 유전자를 포함하고 있는 균주를 선별하였고 PCR과 염기서열분석을 통해 최종적으로 carbapenemase 유전형을 확인했다. 한편 REP-PCR 방법으로 균주간의 clonality를 분석했다. 본 연구에서 A. baumannii 균주는 분석된 모든 항균제에 대해 높은 내성을 나타냈으나 non-A. baumannii 균주는 분석된 항균제 중 aztreonam과 cefotaxime을 제외한 항균제에 모두 감수성을 보였다. A. baumannii 51 균주는 $bla_{OXA-51}$ 유전자를 가지고 있었으며 그 중 37(72.5%)균주는 $bla_{OXA-23}$ 유전자도 동시에 가지고 있었다. 본 연구에서 39 균주의 다제내성 A. baumannii 가 분리되었는데 그 중 37균주가 $bla_{OXA-23}$ 유전자를 가지고 있었다. $bla_{OXA-23}$ 유전자를 포함하고 있는 균주들은 I (n=22) 형 또는 II (n=15) 형의 REP-PCR band 패턴을 보였는데 이는 대전에 위치한 일개의 대학병원에 $bla_{OXA-23}$ 유전자를 포함하고 있는 다제내성 균주들이 수평 확산 되어 있음을 의미한다. 다제내성 A. baumannii 균주에 의한 감염 및 집락화를 막기 위해서는 지속적으로 내성을 유발하는 인자를 조사하고 MDR균주의 출현 및 확산을 감시할 필요가 있을 것으로 사료된다.

• Journal of Microbiology and Biotechnology
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• 제26권2호
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• pp.394-401
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• 2016

Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9) system, a genome editing technology, was shown to be versatile in treating several antibiotic-resistant bacteria. In the present study, we applied the CRISPR/Cas9 technology to kill extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. ESBL bacteria are mostly multidrug resistant (MDR), and have plasmid-mediated antibiotic resistance genes that can be easily transferred to other members of the bacterial community by horizontal gene transfer. To restore sensitivity to antibiotics in these bacteria, we searched for a CRISPR/Cas9 target sequence that was conserved among >1,000 ESBL mutants. There was only one target sequence for each TEM- and SHV-type ESBL, with each of these sequences found in ~200 ESBL strains of each type. Furthermore, we showed that these target sequences can be exploited to re-sensitize MDR cells in which resistance is mediated by genes that are not the target of the CRISPR/Cas9 system, but by genes that are present on the same plasmid as target genes. We believe our Re-Sensitization to Antibiotics from Resistance (ReSAFR) technology, which enhances the practical value of the CRISPR/Cas9 system, will be an effective method of treatment against plasmid-carrying MDR bacteria.

• The Korean journal of internal medicine
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• 제39권3호
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• pp.448-457
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• 2024

Background/Aims: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. Methods: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. Results: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). Conclusions: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.

• 한국수산과학회지
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• 제49권6호
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• pp.800-806
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• 2016

In total, 151 Escherichia coli isolates from Ruditapes philippinarum in Gomso Bay were analyzed for their susceptibility to 18 different antimicrobial agents and for genes associated with virulence. For virulence genes, each strain of the isolates was positive for the enterotoxigenic E. coli (ETEC)-specific heat-stable toxin (estA), enteroinvasive E. coli (EIEC)-specific invasion-associated locus (iaa) gene and enteropathogenic E. coli (EPEC)-specific attaching and effacing (eae) gene. According to a disk diffusion susceptibility test, resistance to ampicillin was most prevalent (23.2%), followed by resistance to amoxicillin (22.5%), ticarcillin (20.5%), tetracycline (18.5%), nalidixic acid (12.6%), ciprofloxacin (10.6%), streptomycin (9.9%), and chloramphenicol (6.6%). More than 35.8% of the isolates were resistant to at least one antimicrobial agent, and 19.9% were resistant to four or more classes of antimicrobials; these were consequently defined as multidrug resistant. Minimum inhibitory concentration (MIC) ranges for the antimicrobial resistance of the 15 different antimicrobial agents of 54 E. coli strains were confirmed by varying the concentrations from $32-2,048{\mu}g/mL$. Overall, these results not only provide novel insights into the necessity for seawater and R. philippinarum sanitation in Gomso Bay but they also help to reduce the risk of contamination by antimicrobial-resistant bacteria.

• 생약학회지
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• 제47권2호
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• pp.122-127
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• 2016

Methicillin-Resistant Staphylococcus aureus(MRSA) is a multidrug-resistant(MDR) strain. (+)-Usnic acid(UA) is uniquely found in lichens, and is especially abundant in genera such as Usnea and Cladonia. UA has antimicrobial activity against human and plant pathogens. Therefore, UA may be a good antibacterial drug candidate for clinical development. In search of a natural products capable of inhibiting this multidrug-resistant bacteria, we have investigated the antimicrobial activity of UA against 17 different strains of the bacterium. In this study, the effects of a combination of UA and permeable agents against MRSA were investigated. For the measurement of cell wall permeability, UA with concentration of Ethylenediaminetetraacetic acid(EDTA) was used. In the other hand, Sodium azide($NaN_3$) was used as inhibitors of ATPase. Against the 17 strains, the minimum inhibitory concentrations(MICs) of UA were in the range of $7.81-31.25{\mu}g/ml$. EDTA or $NaN_3$ cooperation against MRSA showed synergistic activity on cell wall. UA and in combination with EDTA and $NaN_3$ could lead to the development of new combination antibiotics against MRSA infection.