• Title/Summary/Keyword: drug-resistance gene

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Drug Resistance in Fish-Pathogenic Bacteria

  • Aoki, Takashi
    • Journal of fish pathology
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    • v.6 no.1
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    • pp.57-64
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    • 1993
  • The properties and DNA structures of R plasmids differ depending on the species of the fish-pathogens Aeromonas hydrophila, A. salmonicida, Edwardsiella tarda, Enterococcus seriolicida, Pasteurella piscicida and Vibrio anguillarum. However, some R plasmids with the same resistance markers in similar DNA structures were found in A. hydrophila and E. tarda, as well as in A. hydrophila and A. salmonicida. R plasmids from V. anguillarum were classified into three groups according to their DNA structures. The first group was detected before 1977, the second from 1980 to 1983, and the third from 1989 to 1991. R plasmids have been retained within P. piscieida having the same DNA structures and detected at various locations and times. E. seriolicida strains carrying the same R plasmids, which were encoded with resistance to macrolide antibiotics(MLs), lincomycin(LIM), and TC, and to MLs, LIM, and CP. were distributed in yellowtail farms in various districts. The chloramphenicol-resistance(cat) gene of the R plasmids of P. piscicida was classified as CAT type I. The cat of the R plasmids of E, tarda. A. salmonicida was classified as type II. The cat of R plasmids of V. anguillarum was classified into two types. One type detected before 1977, was classified as CAT IV and the other type, detected after 1980, was classified as CAT II. Tetracycline-resistance (tet) V. anguillarum, isolated before 1977 and after 1981, was classified as Tet B and Tet G, respectively. The class D tet gene was widely distributed in R plasmids from fish-pathogens A. hydrophila, E. tarda, P. piscicida, and also V. anguillarum isolated after 1989.

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Emergence of macrolide resistance and clinical use of macrolide antimicrobials in children (Macrolide계 항균제 내성 출현과 소아에서의 임상적 적용)

  • Choi, Eun Hwa
    • Clinical and Experimental Pediatrics
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    • v.51 no.10
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    • pp.1031-1037
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    • 2008
  • Macrolide antimicrobial agents including erythromycin, roxithromycin, clarithromycin, and azithromycin are commonly used in the treatment of respiratory tract infections in children. Newer macrolides that have structural modifications of older drug erythromycin show improved change in the spectrum of activity, dosing, and administration. However, recent studies reported that increasing use of macrolide antibiotics is the main force driving the development of macrolide resistance in streptococci. In particular, azithromycin use is more likely to select for macrolide resistance with Streptococcus pneumoniae than is clarithromycin use, a possible reflection of its much longer half life. Recently, erythromycin resistance rates of S. pneumoniae and Streptococcus pyogenes are rapidly increasing in Korea. Two main mechanisms of acquired macrolide resistance have been described, altered binding site on the bacterial ribosome encoded by the ermB gene and active macrolide efflux pump encoded by the mef gene. Relationship between the susceptibility of S. pneumoniae and the response to macrolides has been shown in studies of acute otitis media, but less clear in cases of pneumonia. This article reviews the spectrum of activity, pharmacokinetic properties, mechanisms of action and resistance, and clinical implication of resistance on the treatment of respiratory tract infections in children.

Analysis of Class 1 Integrons in Imipenem-resistant Pseudomonas aeruginosa

  • Sung, Ji Youn
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.2
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    • pp.68-74
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    • 2011
  • Pseudomonas aeruginosa is an aerobic, Gram-negative, glucose-nonfermenting bacterium, which has emerged as a serious opportunistic pathogen. Recently, outbreaks of carbapenem resistant P. aeruginosa give rise to significant therapeutic challenges for treating nosocomial infections. The genes of metallo-${\beta}$-lactamase (MBL), a powerful carbapenemase, are carried as a part of the mobile gene cassettes inserted into integrons playing an important role in rapid dissemination of antibiotic resistance genes among bacterial isolates. In this study, we investigated the prevalence of integron in imipenem resistant P. aeruginosa isolates. A total of 61 consecutive, non-duplicate, and imipenem resistant P. aeruginosa strains were isolated from a university hospital in the Chungcheong province of Korea. We employed repetitive extragenic palindromic sequence-based PCR (rep-PCR) method for the selection of clonally different P. aerusinosa strains. PCR and DNA sequencing were conducted for the detection of integrons. Twenty-one clonally different P. aeruginosa strains were isolated. Only one (P28) of the strains harbored $bla_{VIM-2}$ that was found as gene cassettes in class 1 integrons. Four of 21 carbapenem resistant P. aeruginosa strains harbored class 1 integron containing aminoglycoside resistance determinant. All of the integrons detected in the study contained more than one resistance gene cassette, which can mediate resistance to multiple antibiotics. To prevent further spreading of the multi-drug resistant P. aeruginosa, conseguent monitoring and clinical polices are required.

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Tamoxifen Resistance and CYP2D6 Copy Numbers in Breast Cancer Patients

  • Motamedi, Sahar;Majidzadeh, Keivan;Mazaheri, Mahta;Anbiaie, Robab;Mortazavizadeh, Seyed Mohammad Reza;Esmaeili, Rezvan
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6101-6104
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    • 2012
  • Background: Breast cancer accounts about one million from total annual ten million new diagnosed cases of neoplasia worldwide and is the main cause of death due to cancer in women. Tamoxifen is the most popular selective estrogen receptor modulator used in anti estrogen treatments. Tamoxifen must be converted into its metabolite endoxifen for biologic effects; this conversion process is catalysed by highly polymorphic cytochrome P450 2D6 (CYP2D6). This study surveyed copy number variation of the CYP2D6 gene and its possible correlation with Tamoxifen resistance in breast cancer patients. Methods: This case control study was performed on samples taken from 79 patients with breast cancer who used tamoxifen in Yazd and Tehran Cities, Iran. Real time reactions were conducted for 10 healthy samples using the comparative $C_t$ (Cycles threshold) method, each pair of genes being compared and samples with ratios around 1 were taken as control samples. Proliferation reactions were done by Real-Time PCR ABI Prism 7500. All registered data were transformed into SPSS 15 program and analyzed. Results: Efficiency of PCR for both CYP2D6 and ALB genes was 100%. From all 23 drug resistant patients 21.7% had one copy, 47.8% two copies and 30.4% had three copies. Also from all 56 drug sensitive patients, 26.8% had one copy, 51.8% two copies and 21.4% had three copies. The percentage of patients with one and two copies was similar between two groups but patients with three copies were more likely to belong to the drug resistant group more. Odd ratios for one and two copies were 0.759 and 0.853 respectively, indicating possible protective effects while that for three copies was 1.604. Conclusions: Based on our study there is no significant link between CYP2D6 gene copy numbers and tamoxifen resistance in women with breast cancer. But more studies considering other influencing factors appear warranted.

Prevelance of Common YMDD Motif Mutations in Long Term Treated Chronic HBV Infections in a Turkish Population

  • Alagozlu, Hakan;Ozdemir, Ozturk;Koksal, Binnur;Yilmaz, Abdulkerim;Coskun, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5489-5494
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    • 2013
  • In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

Characteristics of Ampicillin-Resistant Vibrio spp. Isolated from a West Coastal Area of Korean Peninsula (서해안에서 분리한 암피실린 내성 비브리오속 세균의 특성)

  • Lee, Han-Woong;Lim, Suk-Kyung;Kim, Mal-Nam
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.42 no.1
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    • pp.20-25
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    • 2009
  • Thirty-eight Vibrio spp. were isolated from the sea waters harvested from the 22 stations located on the west coast of the Korean peninsula in September 2006. The isolates consisted of V. parahaemolyticus (n=21), V. alginolyticus (n= 16) and V. cholerae non-01 (n=1), among which 35 isolates displayed resistance against two of the tested antibiotics. Among the 38 isolates, 18 isolates exhibited multi-drug resistance against more than four 4 antibiotics. In particular, minimum inhibitory concentration $(MIC)_{50}$ and $MIC_{90}$ of ampicillin-resistant isolates were as high as $2,048{\mu}g{\cdot}mL^{-1}$ and $4,096{\mu}g{\cdot}mL^{-1}$ respectively. $\beta$-lactamase production was examined to analyze the ampicillin-resistance. Some Vibrio spp. isolates produced $\beta$-lactamase, however antibiotics resistance pattern and $\beta$-lactamase production were not clearly related to each other. A genetic relationship between resistance and gene expression was confirmed in the ampicillin-resistant isolates.

ATG5 knockout promotes paclitaxel sensitivity in drug-resistant cells via induction of necrotic cell death

  • Hwang, Sung-Hee;Yeom, Hojin;Lee, Michael
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.3
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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.

Detection of Methicillin-Resistant Staphylococcus aureus by In Vitro Enzymatic Amplification of MecA and FemA Gene (메티실린 내성 황색 포도상 구균에서 mecA, femA 유전자의 임상적 의의)

  • Park, Jung-Eun;Kim, Taek-Sun;Park, Su-Sung;Kim, Eun-Ryoung;Kim, Il-Su;Ann, Il-Young;Kim, Young-Jin;Kim, Jae-Jong;Kang, Sung-Ok;Park, Han-Ho
    • Pediatric Infection and Vaccine
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    • v.3 no.2
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    • pp.133-138
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    • 1996
  • Purpose : In the treatment of MRSA infection, rapid detection of MRSA is extremely important. The mecA gene codes the new drug resistant polypeptides called PBP2' which mediates the clinically relevant resistance to all beta-lactam antibiotics. The identical mecA gene has been found in coagulase-negative staphylococcus with the methicillin-resistant phenotype. On the other hand, the femA gene was absent from coagulase negative staphylococcus strains with the methicillin resistant phenotype. This study is aimed at early detection and definite diagnosis of MRSA. Methods : A total of 24 MRSA strains were studied. All strains were tested for antimicrobial susceptibility and purified DNA. We amplified both mecA and femA genes by PCR in 24 strains. Results : In MRSA all the 16 strains (100%) carried femA gene and 11 strains (68.7%) carried mecA gene. In contrast, in methicillin sensitive staphylococcus all the 8 strains (100%) carried femA and only 3 strains (37.5%) were detected mecA. Conclusions : As results, there are difference in the phenotype and genotype of methicillin resistance by PCR of mecA and femA. Such disparities between methicillin resistance and the presence of mecA gene suggest the presence of control gene of the mecA.

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Studies on the pathogenicity of Salmonella typhimurium isolated from slaughtered pigs in Chonnam area (전남지역 도축돈에서 분리된 Salmonella typhimurium의 병원성에 관한 연구)

  • 정대영;박종태;고홍범
    • Korean Journal of Veterinary Service
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    • v.26 no.1
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    • pp.39-50
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    • 2003
  • Non-typhoidal Salmonella serovars remain a potential threat to human health and many animals including beef cattle, broiler chickens, and pigs which possible sources of non-typhoidal salmonellosis in human. In this study, the cecal contents of slaughtered pigs were examined for Salmonella serovar prevalence. The characteristics of the isolates, including antimicrobial resistance patterns and virulence genes, were studied along with the reference strain S typhimurium ATCC 13311. Out of 640 sample, 137 Salmonella(21.4%) were isolated and their serovar were identified S typhimurium 83 strains(60.6%), S agona 10 strains(7.3%), S schwarzengrund 4 strains(2.9%), S derby 4 strains(2.9%), S ayinde 1 strains(0.7%), and untypable 35 strains(25.5%). All 83 S typhimurium strains(100%) were multi-drug resistance to at least 7 antibiotics, and 20 strains(24.1%) of 83 isolates were R-type ACSSuT. Examination of virulent gene by PCR revealed that 73 S typimurium field isolates(88%) have a invA gene and 24 strains(28.9%) have a spvC gene. Consequently, S typhimurium infection in slaughtered pigs was relatively to appear high prevalence in their herds which suggested that it should be necessary for herd health monitoring and surveillance.

Roles of GST-π and polβ Genes in Chemoresistance of Esophageal Carcinoma Cells

  • Tang, Yue;Xuan, Xiao-Yan;Li, Min;Dong, Zi-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7375-7379
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    • 2013
  • The main aim of this study was to investigate the roles of GST-${\pi}$ and $pol{\beta}$ genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression vectors containing each gene were constructed and transfected into EC9706 cells, and the biological effects of the two genes assessed based on a resistance index. We additionally investigated the in vitro and in vivo anti-resistance effects of GST-${\pi}$ and $pol{\beta}$ genes using recombinant lentiviruses carrying siRNAs against the two genes. Our results showed that upregulation of GST-${\pi}$ and $pol{\beta}$ genes suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while downregulation of these two genes with RNAi technology reverses this chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST-${\pi}$ gene into transplanted cDDP tumors effectively reversed their chemoresistant phenotype. However, the same treatment against the $pol{\beta}$ gene did not lead to significant efficacy against chemoresistance.