• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2001년도 제10차 추계학술대회
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• pp.53-53
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• 2001

• 한국미생물·생명공학회지
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• 제49권4호
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• pp.519-527
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• 2021

본 연구에서는 국내 건강한 산모의 모유에서 분리한 E. faecalis BMSE-HMP 4주의 용혈여부와 다제내성 균에 대한 항용혈 효능 및 항균 효과를 확인하였다. 분리 균주의 효소 활성을 측정 결과, E. faecalis BMSE-HMP 4주는 지질에 대한 가수분해 효소인 esterase 및 esterase lipase에 대한 활성이 우수하였다. 용혈여부를 확인한 결과, 분리균 모두 용혈반응이 나타나지 않았다. 또한 용혈을 일으키는 다제내성 균주에 대한 항용혈 효능을 검토한 결과, S. aureus CCARM 3855에 대한 항용혈 효능은 BMSE-HMP002가 75.71 ± 10.00%로 가장 높았으며, E. coli DC 2 CCARM 0238과 P. aeruginosa CCARM 0223에 대한 항용혈 효능은 BMSE-HMP001이 각각 76.92 ± 2.99%와 87.93 ± 1.93%로 가장 높게 나타났다. 다제내성균 Staphylococcus spp., Escherichia spp., Pseudomonas spp., Salmonella spp., Klebsiella spp. 및 Enterobacter spp.에 대한 항균활성을 검토한 결과, E. faecalis BMSE-HMP 4주는 그람 양성균주와 그람 음성균주에서 모두 항균력을 보였으며, 분리균 4주 중에서는 BMSE-HMP001과 BMSE-HMP002가 가장 우수한 결과를 보였다. 본 연구에서는 모유유래 유산균 E. faecalis BMSE-HMP 4주의 안전성과 다제내성 균에 의한 용혈 및 항균 효과를 검토하여 유용 유산균으로써 가능성을 확인하였으며, Enterococcus 균주는 항생제 내성 유전자 및 독성 유전자가 없는 경우에 한하여 사용이 가능한 것으로 고시된 바와 같이 본 연구에서 분리한 모유유래 유산균 E. faecalis BMSE-HMP 4주의 항생제 내성 및 독성에 대한 추가적인 연구를 통해 안전성에 대한 입증이 필요할 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.320-326
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• 2015

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

• 대한임상검사과학회지
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• 제54권2호
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• pp.119-124
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• 2022

녹농균(Pseudomonas aeruginosa), 대장균(Escherichia coli) 및 포도알균(Staphylococcus aureus)은 기회감염균이다. 또한 이들 세균은 다제내성(Multiple-Drug Resistance, MDR) 세균의 성질을 가지는 것으로 알려져 있다. 녹농균, 대장균, 포도알균에 대한 다양한 효능을 지닌 6가지 발효액의 항균활성을 분석하였다. 발효액을 섭취했을 때 대장균에서 유전적 발현 변화가 일어나는지 알아보기 위해 annealing control primer를 사용하여 유전자발현 분석을 수행하였다. 디스크확산법을 통해 무화과식초와 대봉감식초가 다른 발효액에 비해 억제대의 크기가 가장 크게 나타났고, 토종약초발효소는 항균효과가 없었다. 대장균에 5% 무화과식초를 처리하여 21일간 매일 계대배양하여 Escherichia coli O157:H7 OmpW gene for outer membrane protein W 유전자 발현이 감소하며, Synthetic construct Lao1 gene for L-amino acid oxidase, complete cds 유전자가 발현이 증가함을 확인하였다. 발효액 중에서 특히 무화과식초를 섭취하는 것은 우리 주변에 항상 존재하는 대장균에 대해 방어능력을 더욱 단단하게 가질 수 있음을 의미하며, 나아가 다제내성균에 대한 천연치료제로 유용하게 쓰일 수 있기를 기대한다.

• Journal of Veterinary Science
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• 제25권3호
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• pp.44.1-44.13
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• 2024

Importance: The emergence and rapid increase in the incidence of multidrug-resistant (MDR) bacteria in pig farms has become a serious concern and reduced the choice of effective antibiotics. Objective: This study analyzed the phylogenetics and diversity of antibiotic resistance genes (ARGs) and molecularly identified the source of ARGs in antibiotic-resistant Escherichia coli isolated from pig farms in Banten Province, Indonesia. Methods: Forty-four antibiotic-resistant E. coli isolates from fecal samples from 44 pig farms in Banten Province, Indonesia, were used as samples. The samples were categorized into 14 clusters. Sequencing was performed using the Oxford Nanopore Technologies MinION platform, with barcoding before sequencing with Nanopore Rapid sequencing gDNA-barcoding (SQK-RBK110.96) according to manufacturing procedures. ARG detection was conducted using ResFinder, and the plasmid replicon was determined using PlasmidFinder. Results: Three phylogenetic leaves of E. coli were identified in the pig farming cluster in Banten Province. The E. coli isolates exhibited potential resistance to nine classes of antibiotics. Fifty-one ARGs were identified across all isolates, with each cluster carrying a minimum of 10 ARGs. The ant(3'')-Ia and qnrS1 genes were present in all isolates. ARGs in the E. coli pig farming cluster originated mainly from plasmids, accounting for an average of 89.4%. Conclusions and Relevance: The elevated potential for MDR events, coupled with the dominance of ARGs originating from plasmids, increases the risk of ARG spread among bacterial populations in animals, humans, and the environment.

• Infection and chemotherapy
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• 제50권4호
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• pp.328-339
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• 2018

Background: Pneumococcal disease is a major cause of morbidity and mortality worldwide, especially in patients with comorbidities and advanced age. This study evaluated trends in epidemiology of adult pneumococcal disease in Crete, Greece, by identifying serotype distribution and antimicrobial resistance of consecutive Streptococcus pneumoniae strains isolated from adults during an 8-year time period (2009-2016) and the indirect effect of the infant pneumococcal higher-valent conjugate vaccines 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13). Materials and Methods: Antimicrobial susceptibility was performed by E-test and serotyping by Quellung reaction. Multidrug resistance (MDR) was defined as non-susceptibility to penicillin (PNSP) combined with resistance to ${\geq}2$ non-${\beta}$-lactam antimicrobials. Results: A total of 135 S. pneumoniae strains were isolated from adults during the study period. Twenty-one serotypes were identified with 17F, 15A, 3, 19A, and 11A, being the most common. The coverage rates of PCV10, and PCV13 were 17.8% and 37.8%, respectively. PCV13 serotypes decreased significantly from 68.4% in 2009 to 8.3% in 2016 (P = 0.002). The most important emerging non-PCV13 serotypes were 17F, 15A, and 11A, with 15A being strongly associated with antimicrobial resistance and MDR. Among all study isolates, penicillin-resistant and MDR strains represented 7.4% and 14.1%, respectively. Predominant PNSP serotypes were 19A (21.7%), 11A (17.4%), and 15A (17.4%). Erythromycin, clindamycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin resistant rates were 30.4%, 15.6%, 16.3%, 16.3%, and 1.5%, respectively. Conclusion: Although pneumococcal disease continues to be a health burden in adults in Crete, our study reveals a herd protection effect of the infant pneumococcal higher-valent conjugate vaccination. Surveillance of changes in serotype distribution and antimicrobial resistance among pneumococcal isolates are necessary to guide optimal prevention and treatment strategies.

• Journal of Microbiology and Biotechnology
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• 제32권12호
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• pp.1537-1546
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• 2022

Staphylococcus aureus is a cause of high mortality in humans and therefore it is necessary to prevent its transmission and reduce infections. Our goals in this research were to investigate the frequency of methicillin-resistant S. aureus (MRSA) in Taif, Saudi Arabia, and assess the relationship between the phenotypic antimicrobial sensitivity patterns and the genes responsible for resistance. In addition, we examined the antimicrobial efficiency and application of silver nanoparticles (AgNPs) against MRSA isolates. Seventy-two nasal swabs were taken from patients; MRSA was cultivated on Mannitol Salt Agar supplemented with methicillin, and 16S rRNA sequencing was conducted in addition to morphological and biochemical identification. Specific resistance genes such as ermAC, aacA-aphD, tetKM, vatABC and mecA were PCR-amplified and resistance plasmids were also investigated. The MRSA incidence was ~49 % among the 72 S. aureus isolates and all MRSA strains were resistant to oxacillin, penicillin, and cefoxitin. However, vancomycin, linezolid, teicoplanin, mupirocin, and rifampicin were effective against 100% of MRSA strains. About 61% of MRSA strains exhibited multidrug resistance and were resistant to 3-12 antimicrobial medications (MDR). Methicillin resistance gene mecA was presented in all MDR-MRSA strains. Most MDR-MRSA contained a plasmid of > 10 kb. To overcome bacterial resistance, AgNPs were applied and displayed high antimicrobial activity and synergistic effect with penicillin. Our findings may help establish programs to control bacterial spread in communities as AgNPs appeared to exert a synergistic effect with penicillin to control bacterial resistance.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5619-5625
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• 2012

Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

• Tuberculosis and Respiratory Diseases
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• 제59권2호
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• pp.179-185
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• 2005

배 경 : 다제내성 폐결핵환자에서 폐병소의 근치절제술 후 일차 항결핵제로 구성된 처방으로 치료하였을 때의 성적을 알아보고자 하였다. 방 법 : 전향적 연구로 국립마산결핵병원에서 1998년 2월부터 2004년 12월 사이에 다제내성 폐결핵으로 수술전 HRCT에서 공동을 포함하는 국소적 병소인 것과 수술 중에 절제부위 이외에 잔존병소가 없다고 판단 된 환자 17명에게 수술 후 3HERZS/3HERS/6HER로 투약하고 그 임상적 경과를 살펴보았다. 결 과 : 대상환자들은 약제감수성검사에서 INH, RFP이외에 평균 4가지 항결핵제에 내성을 보였으며, 술 후 균음전은 평균 2일째 이루어졌다. 평균 39개월의 추구관찰 기간 동안 치료를 중단한 1명을 제외한 94%(15/16) 환자에서 치유되었으며 균음전에 실패한 1명과 치료종결하고 약 7년 후에 재발된 1명은 본원의 처방지침에 따라 이차 항결핵제로 처방을 변경 투약하여 모두 균음전에 성공하였다. 결 론 : 국소적 병변을 가진 다제내성결핵 환자에서 병소의 근치절제후 일차 항결핵제로 구성된 처방으로도 양호한 치료성적을 얻을 수 있었다. 하지만 이러한 경험을 일반화하기 위해서는 더 많은 경험과 병소별 결핵균 주의 특성에 관한 연구 등이 필요할 것으로 사료된다.

• Pediatric Infection and Vaccine
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• 제30권1호
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• pp.47-54
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• 2023

최근 광범위 항생제 사용의 증가로 인한 다제내성 그람 음성균의 출현이 전 세계적으로 문제가 되고 있다. 특히 다제내성 녹농균(multidrug-resistant Pseudomonas aeruginosa) 감염의 치료는 어려우며 중환자의 사망률을 증가시키는 원인이 된다. 세프톨로잔-타조박탐(ceftolozane-tazobactam, Zerbaxa^TM)은 5세대 세팔로스포린과 베타락탐 분해효소저해제로 다제내성 녹농균에 의한 복잡성 요로감염과 복잡성 복강내 감염의 치료에 효과가 있는 것으로 입증되었다. 본지에서 저자들은 소아청소년 혈액암 환자에서 발생한 다제내성 녹농균에 의한 균혈증을 세프톨로잔-타조박탐을 사용하여 성공적으로 치료한 국내 첫 번째 사례를 보고하고자 한다.