• Title/Summary/Keyword: drug-resistance gene

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Molecular Epidemiology of Metallo-β-lactamase Producing Pseudomonas aeruginosa Clinical Isolates (임상에서 분리된 Metallo-β-lactamase 생성 Pseudomonas aeruginosa의 분자역학)

  • Choi, Myung-Won
    • Journal of Life Science
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    • v.22 no.9
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    • pp.1268-1276
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    • 2012
  • The emergence and dissemination of carbapenem-resistant bacteria have resulted in limitations of antibiotic treatment and potential outbreaks of metallo-${\beta}$-lactamase (MBL) producing Pseudomonas aeruginosa resistant to carbapenems. In this study, we conducted molecular characterization of the MBL genes of the ${\beta}$-lactam drug-resistant P. aeruginosa and prepared basic data for treatment and prevention of proliferation of antimicrobial-resistant bacterial infections. Forty-two P. aeruginosa isolates of 254 were resistant to imipenem or meropenem. Among the 42 isolates, 28 isolates were positive for the Hodge test, and 23 isolates were positive for the EDTA-disk synergy test (EDST). MBLs were detected in 59.5% (25/42) of P. aeruginosa isolates. Eight isolates harbored $bla_{IMP-6}$, whereas 17 isolates harbored $bla_{VIM-2}$. The $bla_{IMP-6}$ gene was in a class 1 integron containing five gene cassettes: $bla_{IMP-6}$, qac, aacA4, $bla_{OXA-1}$, and aadA1. Some strains that produce IMP-6 and VIM-2 showed epidemiological relationships. The $bla_{IMP-6}$ gene in carbapenem-resistant P. aeruginosa showed an identical pattern to a gene cassette that was reported at a hospital in Daegu, Korea. Therefore, MBL-producing P. aeruginosa is already endemic in the community. We are concerned that the existence of carbapenem-resistant bacteria containing the blaMBL gene may increase pressure on antibiotic selection when treating infections. We believe that we should select appropriate antibiotics based on the antibiotic susceptibility test and continue the research to prohibit the emergence and spread of antibiotics resistant bacteria.

A Study of Ni-resistant bacteria isolated from gingival crevicular fluid on the patients wearing Ni-Cr alloy prosthesis (In terms of molecular biological aspects) (니켈-크롬 합금 보철물 주위 치은열구 내에서 발견된 니켈 내성 균주에 관한 분자생물학적 연구)

  • Chae, Young-Ah;Woo, Yi-Hyung;Choi, Boo-Byung;Choi, Dae-Gyun;Lee, Sung-Bok;Kwon, Kung-Rock
    • The Journal of Korean Academy of Prosthodontics
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    • v.37 no.6
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    • pp.741-755
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    • 1999
  • As a material of metal-ceramic prosthesis, nickel as a form of Ni-Cr alloy has been used for many dental prostheses in many cases. However, several problems in use of the alloy have been revealed (ex : tissue stimulation, skin allergy, hypersensitivity, cytotoxicity and carcinogenecity). Little is known about nickel with respect to the relationship between Ni-prosthesis and gaining of Ni-resistance in oral microorganisms. The present study was undertaken to check wheather use of Ni-prosthesis leads to occurrence of Ni-resistant microorganisms. So this study may suggest the possible relationships between the oral microorganisms and nickel-resistance in oral environment. Bacteria were isolated from the gingival crevicular fluid on the pateints wearing Ni-Cr prosthesis. The isolated bacteria were tested for their Ni-resistance in nickel containing media at different concentration from 3mM to 110mM. E. coli HB101 was used as control. The Ni-resistant bacteria were isolated and biochemically identified. The Ni-resistant bacteria were tested several bio-chemical, molecular-biological tests. Performed tests were ; measuring the growth curve, antibiotic test, growth ability test in liquid media, isolation of the chromosome and plasmid, digestion of DNA by restriction enzyme, electrophoresis of chromosome and plasmid DNA, identification of Ni-resistant genes by the DNA hybridization. The results were as follows: 1) The bacteria isolated from gingival crevicular fluid on the patients wearing Ni-Cr alloy pros-thesis showed nickel-resistance. 2) The isolated microorganisms grew at nickel containing media of high concentrations (60mM-110mM). 3) Based on the biochemical tests, the isolated microorganisms were identified as Enterococcus faecalis(13 cases), Klebsiella pneumoniae(1 case) and Enterobacter gergeviae(1 case). 4) Enterococcus faecalis expressed not only nickel resistance but also the multi-drug resistance to several antibiotics ; chloramphenicol, kanamicin, streptomycin, lincomycin, clindamycin. However, all strain showed the sensitivity against the tetracycline. 5) DNA hybridization result suggest that there is no homology between the previousely known gene of nickel resistance in Klebsiella pneumoniae and chromosomal DNA of Enterococcus faecalis.

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Prevalence and Classification of Escherichia coli Isolated from bibimbap in Korea (비빔밥에서 분리한 대장균의 오염도 조사 및 특성 연구)

  • Lee, Da-Yeon;Lee, Joo-Young;Wang, Hae-Jin;Shin, Dong-Bin;Cho, Yong-Sun
    • Korean Journal of Food Science and Technology
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    • v.47 no.1
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    • pp.126-131
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    • 2015
  • Pathogenic Escherichia coli is recognized as an important cause of diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome worldwide. This study was conducted to investigate the prevalence E. coli contamination in the Korean traditional food bibimbap. E. coli were isolated from 84 of 1142 (7.3%) bibimbap investigated from 2005 to 2011. Antibiotic resistance profiling demonstrated that 6 of the 84 isolates (7.2%) showed multiple drug resistance. Fifteen virulence genes specific for pathogenic E. coli such as Shiga toxin-producing E. coli (STEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), and enteroaggregative E. coli (EAEC) were examined by multiplex PCR for mixed bacterial cultures derived from bibimbap samples. The EPEC virulence gene (ent) was detected in 5 strains (5.9%), while ETEC, EAEC, and EIEC were not detected. STEC serotypes O103 (1.2%), O91 (1.2%), and O128 (6.0%) were found, but other serogroups such as O26, O157, O145, O111 and O121 were not detecded. Automated Repetitive-Sequence-Based PCR analysis showed different patterns.

Gilteritinib Reduces FLT3 Expression in Acute Myeloid Leukemia Cells

  • Thi Lam Thai;Sun-Young Han
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.577-581
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    • 2024
  • Acute myeloid leukemia (AML) is a genetically diverse and challenging malignancy, with mutations in the FLT3 gene being particularly common and deleterious. Gilteritinib, a potent FLT3 inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory AML with FLT3 mutations. Although gilteritinib was developed based on its inhibitory activity against FLT3 kinase, it is important to understand the precise mechanisms of its antileukemic activity in managing drug resistance and discovering biomarkers. This study was designed to elucidate the effect of gilteritinib on the FLT3 expression level. The results showed that gilteritinib induced a dose-dependent decrease in both FLT3 phosphorylation and expression. This reduction was particularly pronounced after 48 h of treatment. The decrease in FLT3 expression was found to be independent of changes in FLT3 mRNA transcription, suggesting post-transcriptional regulatory mechanisms. Further studies were performed in various AML cell lines and cells with both FLT3 wild-type and FLT3 mutant exhibited FLT3 reduction by gilteritinib treatment. In addition, other FLT3 inhibitors were evaluated for their ability to reduce FLT3 expression. Other FLT3 inhibitors, midostaurin, crenolanib, and quizartinib, also reduced FLT3 expression, consistent with the effect of gilteritinib. These findings hold great promise for optimizing gilteritinib treatment in AML patients. However, it is important to recognize that further research is warranted to gain a full understanding of these mechanisms and their clinical implications in the context of FLT3 reduction.

Overexpression of Ubiquitin and Amino Acid Permease Genes in Association with Antimony Resistance in Leishmania tropica Field Isolates

  • Kazemi-Rad, Elham;Mohebali, Mehdi;Erfan, Mohammad Bagher Khadem;Hajjaran, Homa;Hadighi, Ramtin;Khamesipour, Ali;Rezaie, Sassan;Saffari, Mojtaba;Raoofian, Reza;Heidari, Mansour
    • Parasites, Hosts and Diseases
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    • v.51 no.4
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    • pp.413-419
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    • 2013
  • The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime$^{(R)}$) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in resistant isolates compared to sensitive ones. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance.

A STUDY OF NI-RESISTANT BACTERIA ISOLATED FROM GINGIVAL CREVICULAR FLUID ON THE PATIENTS WEARING NI-CR ALLOY PROSTHESIS (IN TERMS OF MOLECULAR BIOLOGICAL ASPECTS) (니켈-크롬 합금 보철물 주위 치은 열구내에서 발견된 니켈 내성 균주에 관한 분자생물학적 연구)

  • Chae Young-Ah;Woo Yi-Hyung;Kwon Kung-Rock
    • The Journal of Korean Academy of Prosthodontics
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    • v.41 no.2
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    • pp.207-222
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    • 2003
  • As a material of metal-ceramic prosthesis, nickel as a form of Ni-Cr alloy has been used for many dental prostheses in many cases. However, several problems in use of the alloy have been revealed (ex ; tissue stimulation, skin allergy, hypersensitivity cytotoxicity and carcinogenecity). Little is known about nickel with respect to the relationship between Ni-prosthesis and gaining of Niresistance in oral microorganisms. The present study was undertaken to check whether use of Ni-prosthesis leads to occurrence of Ni-resistant microorganisms. So this study may suggest the possible relationships between the oral microorganisms and nickel-resistance in oral environment. Bacteria were isolated from the gingival crevicular fluid on the patients wearing Ni-Cr prosthesis. The isolated bacteria were tested fir their Ni-resistance in nickel containing media at different concentration from 3mM to 110mM. E. coli HB101 was used as control. The Ni-resistant bacteria were isolated and biochemically identified. The Ni-resistant bacteria were tested several biochemical, molecular-biological tests. Performed tests were : measuring the growth curve, antibiotic test, growth ability test in liquid media, isolation of the chromosome and plasmid, digestion of DNA by restriction enzyme, electrophoresis of chromosome and plasmid DNA, identification of Ni-resistant genes by the DNA hybridization. The results were as follows 1) The bacteria isolated from gingival crevicular fluid on the patients wearing Ni-Cr alloy prosthesis showed nickel-resistance. 2) The isolated microorganisms grew at nickel containing media of high concentrations (60mM-110mM). 3) Based on the biochemical tests, the isolated microorganisms were identified as Enterococcus faecalis(13 cases), Klebsiella pneumoniae(1 case) and Enterobacter gergoviae(1 case). 4) Enterococcus faecalis expressed not only nickel resistance but also the multi-drug resistance to several antibiotics ; chloramphenicol, kanamicin, streptomycin, lincomycin, clindamycin, However, all strain showed the sensitivity against the tetracycline. 5) DNA hybridization result suggests that there is no homology between the previously known gene of nickel resistance in Klebsiella pneumoniae and chromosomal DNA of Enterococcus faecalis.

Downregulated microRNAs in the colorectal cancer: diagnostic and therapeutic perspectives

  • Hernandez, Rosa;Sanchez-Jimenez, Ester;Melguizo, Consolacion;Prados, Jose;Rama, Ana Rosa
    • BMB Reports
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    • v.51 no.11
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    • pp.563-571
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    • 2018
  • Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

Distribution of Antibiotic-Resistant Bacteria in the Livestock Farm Environments

  • Kim, Youngji;Seo, Kun-Ho;Kim, Binn;Chon, Jung-Whan;Bae, Dongryeoul;Yim, Jin-Hyeok;Kim, Tae-Jin;Jeong, Dongkwan;Song, Kwang-Young
    • Journal of Dairy Science and Biotechnology
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    • v.39 no.1
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    • pp.1-8
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    • 2021
  • The surroundings of livestock farms, including dairy farms, are known to be a major source of development and transmission of antibiotic-resistant bacteria. To control antibioticresistant bacteria in the livestock breeding environment, farms have installed livestock wastewater treatment facilities to treat wastewater before discharging the final effluent in nearby rivers or streams. These facilities have been known to serve as hotspots for inter-bacterial antibiotic-resistance gene transfer and extensively antibiotic-resistant bacteria, owing to the accumulation of various antibiotic-resistant bacteria from the livestock breeding environment. This review discusses antibiotic usage in livestock farming, including dairy farms, livestock wastewater treatment plants as hotspots for antibiotic resistant bacteria, and nonenteric gram-negative bacteria from wastewater treatment plants, and previous findings in literature.

New Targeted Therapy for Non-Small Cell Lung Cancer

  • Eun Ki Chung;Seung Hyun Yong;Eun Hye Lee;Eun Young Kim;Yoon Soo Chang;Sang Hoon Lee
    • Tuberculosis and Respiratory Diseases
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    • v.86 no.1
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    • pp.1-13
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    • 2023
  • Lung cancer ranks first in cancer mortality in Korea and cancer incidence in Korean men. More than half of Korean lung cancer patients undergo chemotherapy, including adjuvant therapy. Cytotoxic agents, targeted therapy, and immune checkpoint inhibitors are used in chemotherapy according to the biopsy and genetic test results. Among chemotherapy, the one that has developed rapidly is targeted therapy. The National Comprehensive Cancer Network (NCCN) guidelines have been updated recently for targeted therapy of multiple gene mutations, and targeted therapy is used not only for chemotherapy but also for adjuvant therapy. While previously targeted therapies have been developed for common genetic mutations, recently targeted therapies have been developed to overcome uncommon mutations or drug resistance that have occurred since previous targeted therapy. Therefore, this study describes recent, rapidly developing targeted therapies.

Comparison of PCR-Line Probe and PCR-SSCP Methods for the Detection of Rifampicin Resistant Mycobacterium Tuberculosis (Rifampicin 내성 결핵균의 검출에 있어서 PCR-line Probe법과 PCR-SSCP법의 비교)

  • Kim, Ho-Joong;Suh, Gee-Young;Chung, Man-Pyo;Kim, Jong-Won;Shim, Tae-Sun;Choi, Dong-Chull;Kwon, O-Jung;Rhee, Chong-H;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.4
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    • pp.714-722
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    • 1998
  • Background: Rifampicin (RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant (MDR) tuberculosis. RPoB gene encodes the $\beta$-subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And the mutations of rpoB gene have been found in about 96% of rifampicin resistant clinical isolates of M. tuberculosis. So in order to find a rapid and clinically useful diagnostic method in identifying the RFP resistance, we compared the PCR -line probe method with PCR-SSCP for the detection of the rpoB gene mutation in cultured M. tuberculosis. Methods: 45 clinical isolates were collected from patients who visited Sung Kyun Kwan University Hospital. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. 33 were rifampicin resistant and 12 were rifampicin susceptible. The susceptibility results were compared with the results of the PCR-BSCP and PCR-line probe method. Results: We could find rpoB mutations in 27/33(81.8%) RFP-resistant strains by PCR-line probe method, and in 23/33 (69.7%) by PCR-SSCP and there was no significant difference between two methods. There was no mutation in rifampicinn susceptible strains by both methods. Conclusion: PCR-line probe method would be a rapid, sensitive and specific method for the detection of rifampicin resistant Mycobacterium tuberculosis.

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