• 한국동물위생학회지
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• 제45권3호
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• pp.181-189
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• 2022

Streptococcus is one of the major pathogen groups inducing bovine mastitis. The aim of this study was to investigate the antimicrobial resistance patterns of Streptococcus species isolated from bovine mastitis milk samples in Korea from 2016 to 2021. In total, 181 (10.3%) Streptococcal isolates were collected from 1,761 quarter milk samples at 122 farms; S. uberis 39.2% (n=71), S. dysgalactiae 29.3% (n=53), S. equinus 9.9% (n=18), S. suis 6.1% (n=11), S. parauberis 4.4% (n=8), S. lutetiensis 3.9% (n=7), others 7.2% (n=13). However, S. agalactiae was not isolated. The isolates showed the highest resistance rate to tetracycline (55.2%) followed by erythromycin (45.3%) and pirlimycin (36.5%). In contrast, all isolates were susceptible to ceftiofur, cephalothin, penicillin/novobiocin, and only single S. equinus isolate was resistant to both ampicillin and penicillin. Of 181 isolates, 64 (35.4%) were multidrug resistance (MDR). The resistance to pirlimycin of S. uberis (73.2%) was much higher than that of other species (0~36.4%). All S. suis isolates were resistance to tetracycline. S. dysgalactiae showed lower resistance to erythromycin, pirlimycin and tetracycline than S. uberis and S. suis. The rate of MDR was relatively higher among S. uberis (73.2%) than among S. suis (36.4%), S. dysgalactiae (15.1%), others (0%). In conclusion, antimicrobial resistance in Streptococcus spp. should be regularly examined for appropriate therapies because the resistance patterns were various among the individual species.

• The Korean Journal of Physiology and Pharmacology
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• 제24권3호
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• pp.233-240
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• 2020

Autophagy regulators are often effective as potential cancer therapeutic agents. Here, we investigated paclitaxel sensitivity in cells with knockout (KO) of ATG5 gene. The ATG5 KO in multidrug resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr) was generated using the CRISPR/Cas9 technology. The qPCR and LC3 immunoblot confirmed knockout of the gene and protein of ATG5, respectively. The ATG5 KO restored the sensitivity of Ras-NIH 3T3/Mdr cells to paclitaxel. Interestingly, ATG5 overexpression restored autophagy function in ATG5 KO cells, but failed to rescue paclitaxel resistance. These results raise the possibility that low level of resistance to paclitaxel in ATG5 KO cells may be related to other roles of ATG5 independent of its function in autophagy. The ATG5 KO significantly induced a G₂/M arrest in cell cycle progression. Additionally, ATG5 KO caused necrosis of a high proportion of cells after paclitaxel treatment. These data suggest that the difference in sensitivity to paclitaxel between ATG5 KO and their parental MDR cells may result from the disparity in the proportions of necrotic cells in both populations. Thus, our results demonstrate that the ATG5 KO in paclitaxel resistant cells leads to a marked G₂/M arrest and sensitizes cells to paclitaxel-induced necrosis.

• 한국미생물·생명공학회지
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• 제32권1호
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• pp.47-51
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• 2004

암세포가 특정 항암제에 의해 내성을 획득하면 구조가 상이한 타 항암제에도 교차내성을 나타내는 이른바 암세포의 다약제 내성이 암 화학요법에 있어서 가장 심각한 문제가 되고 있다. 본 연구에서는 다약제 내성 암세포주인 CL02 세포를 이용하여 cellulose 용해성 점액세균인 Sorangium cellulosum의 60여종의 균주를 대상으로 다약재 내성 암세포에 유효한 항암물질을 탐색하는 과정에서, 균주 JW1006의 대사산물에서 강한 증식억제 활성을 발견하고 그 활성 본체로서 macrolide계 화합물인 Disorazoles $A_1$과 $A_2$를 분리하였다 Disorazoles $A_1$과 $A_2$는 인체기원의 암세포에 대해 모두 강한 세포독성($IC_{50}$ ＜0.04 ng/$m\ell$)을 나타낼 뿐 아니라 다약제내성 세포주인 CL02와 cisplatin내성 세포주인 CP70에 대해서 감수성 세포주와 동일한 활성을 나타내어 다약제 내성을 극복하는 우수한 활성 물질임을 확인하였다

• Asian Pacific Journal of Cancer Prevention
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• 제16권15호
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• pp.6663-6668
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• 2015

Background: Treatment failure in leukemia is due to either pharmacokinetic resistance or cell resistance to drugs. Materials and Methods: Gene expression of multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and low resistance protein (LRP) was assessed in 45 pediatric ALL cases and 7 healthy controls by real time PCR. The expression was scored as negative, weak, moderate and strong. Results: The male female ratio of cases was 2.75:1 and the mean age was 5.2 years. Some 26/45 (58%) were in standard risk, 17/45(38%) intermediate and 2/45 (4%) in high risk categorie, 42/45 (93%) being B-ALL and recurrent translocations being noted in 5/45 (11.0%). Rapid early response (RER) at day 14 was seen in 37/45 (82.3%) and slow early response (SER) in 8/45 (17.7%) cases. Positive expression of MDR-1, LRP and MRP was noted in 14/45 (31%), 15/45 (33%) and 27/45 (60%) cases and strong expression in 3/14 (21%), 11/27 (40.7%) and 8/15 (53.3%) cases respectively. Dual or more gene positivity was noted in 17/45 (38%) cases. 46.5 % (7/15) of LRP positive cases at day 14 were in RER as compared to 100% (30/30) of LRP negative cases (p<0.05). All 8 (100%) LRP positive cases in SER had strong LRP expression (p=<0.05). Moreover, only 53.3% of LRP positive cases were in haematological remission at day 30 as compared to 100% of LRP negative cases (p=<0.05). Conclusions: Our study indicated that increased LRP expression at diagnosis in pediatric ALL predicts poor response to early treatment and hence can be used as a prognostic marker. However, larger prospective studies with longer follow up are needed, to understand the clinical relevance of drug resistance proteins.

• Journal of Veterinary Science
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• 제21권1호
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• pp.2.1-2.14
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• 2020

The emergence of livestock-associated (LA)-methicillin-resistant Staphylococcus aureus (MRSA) in livestock animal has become a significant zoonotic concern. In the present study, we investigated nationwide prevalence of LA-MRSA across pork production chain including pig farms, slaughterhouses, and retail markets. A total of 40 MRSA strains were isolated during the investigation and the overall prevalence of MRSA was 3.4% (n = 37), 0.6% (n = 2), and 0.4% (n = 1) in pig farms, slaughterhouses, and retail markets, respectively. Multilocus sequence typing analyses revealed that the 2 most significant clonal lineages in pork production chain in Korea were ST398 (n = 25) and ST541 (n = 6). All of the 40 MRSA isolates were further characterized to investigate key genotypic and phenotypic correlates associated with the emergence and spread of clonal complex 398 (CC398; ST398, and ST541) LA-MRSA. Although the prevalence of swine-associated MRSA was still relatively low and mostly restricted to pig farms, multidrug-resistant CC398 LA-MRSA isolates with new spa types (t18102 and t18103) were identified as a major clonal lineage. The CC398 LA-MRSA strains tended to exhibit increased levels of multiple drug resistance (MDR) phenotype compared with non-CC398 MRSA strains. Of note, in comparison with non-CC398 MRSA isolates, CC398 LA-MRSA isolates exhibited significantly enhanced tetracycline (TET) and zinc resistance. These findings suggested that co-selection pressure associated with MDR phenotype, especially TET resistance, and zinc resistance may have played a significant role in the emergence and persistence of CC398 LA-MRSA in pig farms in Korea.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.490-496
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• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5451-5454
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• 2012

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5361-5365
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• 2013

The objective of this study was to evaluate the influence of a genetic variant in the multidrug resistance 1 gene (MDR1) on hepatocellular carcinoma (HCC) risk. This case-control study was conducted in a Chinese population of 645 HCC cases and 658 cancer-free controls. The genotype of the c.3751G>A genetic variant in the MDR1 gene was investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Our data demonstrated significantly differences detected in the allelic and genotypic frequencies between HCC cases and those of cancer-free controls. Association analyses indicated that there were statistically increased risk of HCC in the homozygote comparison (AA versus (vs.) GG: OR=2.22, 95% CI 1.51-3.27, ${\chi}^2$=16.90, P<0.001), dominant model (AA/GA vs. GG: OR=1.25, 95% CI 1.00-1.55, ${\chi}^2$=3.98, P=0.046), recessive model (AA vs. GA/GG: OR=2.14, 95% CI 1.47-3.09, ${\chi}^2$=16.68, P<0.001) and allele comparison (A vs. G: OR=1.33, 95% CI 1.13-1.57, ${\chi}^2$=11.66, P=0.001). The allele-A and genotype-AA may contribute to HCC susceptibility. These preliminary findings suggest that the c.3751G>A genetic variant in the MDR1 gene is potentially related to HCC susceptibility in a Chinese Han population, and might be used as a molecular marker for evaluating HCC susceptibility.

• 대한임상검사과학회지
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• 제51권3호
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• pp.301-308
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• 2019

다제내성 P. aeruginosa의 출현과 확산은 전 세계적으로 중요한 문제가 되고 있다. P. aeruginosa에 의한 발병은 일부 몇몇 세포 관련 및 세포외 병독성 인자의 생성에 기인한다. 본 연구에서는 대전지역의 3차 병원에서 분리된 carbapenem 내성 P. aeruginosa를 대상으로 병독성 인자의 분포와 항균제 내성 양상을 조사하였다. 항균제 감수성 시험은 디스크 확산법으로 확인하였고, 병독성 유전자의 분석을 위해 PCR과 염기서열분석을 수행하였다. 또한, 다제내성 P. aeruginosa의 sequence type (ST)은 multilocus sequence typing (MLST)을 통해 확인하였다. 32균주의 carbapenem 내성 P. aeruginosa 중, 14균주(43.8%)가 다제내성이었으며, 주요 ST는 ST235 (10균주, 71.4.%)임을 확인하였다. 병독성 유전자는 32균주 모두에서 확인되었고, 이 중 가장 높은 빈도로 확인된 병독성 유전자는 toxA, plcN, phzM (100.%)이었다. 또한, 32균주는 모두 8개 이상의 병독성 유전자를 가지고 있었으며, 9균주(28.1%)가 15개의 병독성 유전자를 가지고 있었다. exoU 유전자는 다제내성 P. aeruginosa 균주의 71.4%에서 확인되었다. 이러한 결과는 exoU 유전자가 다제내성 P. aeruginosa 균주의 지속성에 대한 예측 표지자가 될 수 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제51권5호
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• pp.409-415
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• 2001

배 경 : 다제내성 폐결핵은 대부분은 획득내성에 의해 발생한다. 그러나 일부분에서 초회내성으로 발생하는데 이러한 환자들은 획득내성으로 인한 환자들과 차이가 있을 것으로 생각된다. 본 연구는 초회내성으로 진단된 다제내성 폐결핵 환자들의 임상적 특징을 조사하여 향후 이들에 대한 효과적인 치료에 지표로 삼고자 한다. 대상 및 방법 : 1995년 1월부터 1998년 12월까지 입원치료를 시행한 초회내성으로 진단된 다제내성 폐결핵 환자 30명을 대상으로 하였다. 임상적 특징을 조사하기 위하여 성별, 연령, 가족력, 균음전화 기간, 내성약제수, 치료약제와 흉부방사선상 NTA 분류를 이용한 병변의 정도 및 공동 유무와 치료기간 등을 조사하였다. 통계적 분석은 흉부방사선상 병변의 정도와 공동의 호전 여부를 윌콕슨 부호 순위 검정법을 이용하였고, Kaplan-Meier 방법으로 1년 및 4년 무병율을 조사하였다. 결 과 : 환자들의 평균나이는 평균 46.6세였고, 남녀비는 1:1이었다. 폐결핵 가족력이 있었던 경우는 6(20%)명이었다. 객담에서 균이 음전된 기간은 평균 2.6개월이었으며, 내성약제의 개수는 평균 7.6개였다. 환자들 중 23(67%)명에서 12개월 이하로 치료하였다. 그리고 초치료 처방으로 치료한 경우는 28(93%)명이었다. 흉부방사선상 병변의 정도와 공동은 치료 후 호전되었다(p<0.05). 총 13명의 환자들 평균 22.6개월간 외래 추적조사 결과 2(15%)명에서 재발을 관찰할 수 있었고, 1년 및 4년 무병율은 85%였다. 결 론 : 초회내성으로 진단된 다제내성 폐결핵의 경우에 있어서 초치료 처방으로 하여 흉부방사선상 병변의 정도와 공동의 호전 여부를 주의 깊게 관찰하면서 9-12개월을 치료한다면 성공적인 결과를 얻을 수 있을 것으로 생각된다.