• Title/Summary/Keyword: mutation rate

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Resistance Determinants and Antimicrobial Susceptibilities of Mupirocin-Resistant Staphylococci Isolated from a Korean Hospital (국내 한 대학병원에서 수집된 Mupirocin 내성 포도알균의 내성 유전자 및 항생물질 감수성 분석)

  • Min, Yu-Hong;Lee, Jong-Seo;Kwon, Ae-Ran;Shim, Mi-Ja;Choi, Eung-Chil
    • Korean Journal of Microbiology
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    • v.48 no.2
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    • pp.93-101
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    • 2012
  • We analyzed mupirocin resistance rates among staphylococcal isolates collected from a Korean hospital in 2003 (100 isolates), 2005 (195 isolates), 2006 (151 isolates), and 2009 (112 isolates). In Staphylococcus aureus, rates of high-level mupirocin resistance (MIC, minimal inhibitory concentration ${\geq}512{\mu}g/ml$) decreased and did not appear since 2005. In contrast, low-level mupirocin resistance (MIC $8-256{\mu}g/ml$) was not detected in 2003 and 2005 but its rates later increased to 6.9% in 2009. Total resistance rates of coagulase-negative staphylococci (CNS) were significantly higher than those of S. aureus. The rates of high-level resistance of CNS increased from 16.0% in 2003 to 31.5% in 2009. The rate of low-level resistance of CNS was 8.0% in 2003 and around 11% later. In all high-level resistant isolates, the ileS-2 gene was detected. All low-level resistant isolates contained the known V588F mutation in ileS gene. Previously unknown mutations such as V458G in S. aureus and D172A, Y490H and I750V in CNS were identified additionally. One S. aureus isolate with high-level resistance was resistant to oxacillin and several topical antibiotics commonly used for the treatment of skin infection. Ten S. aureus isolates with low-level resistance were also resistant to all of these antibiotics except fusidic acid. CNS isolates with high-level (61 isolates) and low-level resistance (27 isolates) exhibited significantly higher resistance rates to these antibiotics than mupirocin-susceptible CNS isolates (167 isolates). In conclusion, prevention of the emergence of mupirocin resistance is necessary for the effective treatment of skin infection by staphylococci.

Antimutagenic and Antitumor Effects of Adenophora triphylla Extracts (잔대 추출물들의 항돌연변이 및 항종양 효과)

  • Ham, Young-An;Choi, Hyun-Jin;Kim, Soo-Hyun;Chung, Mi-Ja;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.1
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    • pp.25-31
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    • 2009
  • This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

Mono-Rifampicin-Resistant Pulmonary Tuberculosis (Rifampicin단독내성 폐결핵)

  • Shim, Tae-Sun;Lee, Ki-Man;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.618-627
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    • 1999
  • Background : Rifampicin (RFP) is a key component of the antituberculous short-course chemotherapy. Usually the RFP resistant M.tuberculosis is also resistant to isoniazid (INH), so the RFP resistance is the marker of multi-drug resistant (MDR) tuberculosis. But unusual cases of mono-RFP-resistant tuberculosis have been recently reported with increasing frequency, especially associated with HIV infection in western countries. Therefore, we conducted a retrospective study to investigate the frequency, causes, and the clinical characteristics of mono-RFP-resistant tuberculosis in Korea. Methods : Of the bacteriologically confirmed and susceptibility-proven 699 pulmonary tuberculosis patients (921 isolates) who visited Asan Medical Center from January 1990 to August 1997, eighteen patients with INH-susceptible and RFP-resistant tuberculosis were evaluated. Previous history of tuberculosis, antituberculous drug compliances, associated systemic illness, drug susceptibility patterns, and clinical outcomes were analysed. And rpoB gene sequencing was done in 6 clinical isolates of M. tuberculosis. Results : The mean age of 18 patients was $43{\pm}14$ years, and the sex ratio is 12:6 (M : F). Sixteen (89%) patients had previous history of tuberculosis. None had diagnosed gastrointestinal disorders, and 2 HIV tests that were performed came out negative. Susceptibility tests were done repeatedly in eleven patients, and six (55%) were mono-RFP resistant repeatedly while five (45%) evolved to MDR tuberculosis. Eight (44%) patients were cured, six (33%) failed, three (17%) were lost to follow-up, and the other one is now on treatment. rpoB gene sequencing showed 5 mutations, codon 531 TCG to TIG mutation in 4 isolates and 526 CAC to TAC in 1 isolate. Conclusion : The clinical characteristics of mono-RFP resistant tuberculosis were similar to that of MDR tuberculosis in Korea where the HIV infection rate is lower than western countries. But some patients with mono-RFP-resistant tuberculous could be cured by primary drug regimens including RFP, suggesting that mono-RFP-resistant tuberculous is a different entity from MDR tuberculosis.

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Therapeutic Efficacy of Adefovir Dipivoxil in Korean Children and Adolescents with Chronic Hepatitis B who have Developed Lamivudine Resistance (Lamivudine 내성 소아 청소년 만성 B형 간염에서 Adefovir의 치료 효과)

  • Hwang, Su-Kyeong;Park, Sun-Min;Choe, Byung-Ho;Kim, Jung-Mi;Kim, Jung-Ok;Kim, Young-Mi;Lee, Ji-Hye;Cho, Min-Hyun;Tak, Won-Young;Kweon, Young-Oh
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.11 no.2
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    • pp.143-149
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    • 2008
  • Purpose: To estimate the long-term therapeutic efficacy and safety of adefovir dipivoxil in children and adolescents with chronic hepatitis B who have developed lamivudine resistance. Methods: Sixteen patients (12 boys and 4 girls; ages 4.3~20.9 years; mean age 14.2 years) with chronic hepatitis B infection resistant to lamivudine therapy received adefovir (0.3 mg/kg/day, maximal dose 10 mg) orally for at least 9 months between March 2004 and April 2008. Each patient was followed up for a mean period of 27 months (range 9~49 months) until April 2008 at Kyungpook National University Hospital in Korea. Therapeutic responses to adefovir were evaluated at 12, 24, 36, and 48 months from the initiation of therapy using the Kaplan-Meier method. Response measurements included ALT normalization, HBV DNA negativization, 2 $log_{10}$ IU/mL decrement of HBeAg titer, HBeAg loss, and HBeAg/Ab seroconversion rate. Results: Three (18.8%) of the 16 patients treated with adefovir showed HBeAg/Ab seroconversion. Kaplan-Meier estimates of cumulative ALT normalization were 12.5% (12 months), 43.8% (24 months), 63.5% (36 months), and 92.7% (48 months), respectively. Cumulative HBV DNA negativization was 6.7%, 30.0%, 45.6%, and 78.2% at 12, 24, 36, and 48 months, respectively. Cumulative 2 $log_{10}$ copies/mL decrement of HBeAg titer was 12.5%, 43.8%, 56.3%, and 86.9% at 12, 24, 36, and 48 months, respectively. Cumulative HBeAg loss and HBeAg/Ab seroconversion were 6.7% (12 months) and 22.2% (24 months), respectively. Conclusion: The long-term therapeutic efficacy of adefovir dipivoxil was favorable in children and adolescents with chronic hepatitis B who had developed lamivudine resistance. The long-term use of adefovir should be safe in children.

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Development of Saccharomyces cerevisiae Strains with High RNA Content (리보핵산을 다량으로 함유하는 Saccharomyces cerevisiae 균주의 개발)

  • Kim, Jae-Sik;Kim, Jin-Wook;Shim, Won;Min, Byoung-Cheol;Kim, Jung-Wan;Park, Kwan-Hwa;Pek, Un-Hua
    • Korean Journal of Food Science and Technology
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    • v.31 no.2
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    • pp.465-474
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    • 1999
  • RNase activity of Saccharomyces cerevisiae ATCC 7754 was investigated to obtain strains with high ribonucleic acid (RNA) content. The yeast strain contained two RNase activities; an acidic RNase with a optima of pH $3{\sim}4$ and an alkaline RNase with a optima pH 9. The acidic RNase activity was inhibited by $0.08\;M\;HgCl_{2}$ most drastically. The alkaline RNase activity was inhibited by 2.0 M NaCl or KCl, while enhanced by addition of $0.05\;M\;CaCl_{2},\;0.02\;M\;ZnSO_{4},\;or\;0.008\;M\;HgCl_{2}$. Various mutants of Saccharomyces cerevisiae ATCC 7754 were isolated by ethylmethane sulfonate (EMS) treatment or $\gamma$-ray/ultra violet irradiation. Among the mutants that were sensitive to high concentration of KCl which inhibits alkaline RNase, B24 was selected for high RNA content per culture volume. Growth characteristics of the mutant were comparable to those of the mother strain with optimum growth at pH $4.5{\sim}5.5$. The mutant accumulated higher content of RNA than the mother strain when glucose was used as the carbon source. However, both growth rate and total RNA content of the mutant were higher in molasses medium than in glucose medium. RNA content of the mutant increased rapidly during the early stage of growth, and then decreased gradually until the culture reached stationary phase by a fed-batch culture in a 5 L jar fermenter. Maximal cell harvest and the final RNA content using the mutant B24 were 69.6 g/L culture broth and 19.8 g/100 g of the dry cell while those using the mother strain were 68 g/L culture broth and 16.1 g/100 g of dry cell, respectively.

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Studies on the Mutation of Aspergillus niger (흑국균(黑麴菌)의 인공변이(人工變異)에 관(關)한 연구(硏究))

  • Park, Yoon-Joong;Sohn, Cheon-Bae
    • Korean Journal of Food Science and Technology
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    • v.14 no.1
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    • pp.72-79
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    • 1982
  • Several mutants were isolated from the parent strain of Aspergillus niger CF: the first mutant strain CF-11 was obtained by UV irradiation, and the second mutant strain CF-21 and CF-22 were from NTG (N-methyl-N'-nitroso-N-nitroso-guanidine) treatment on the CF-11. These mutants were characterized, and their enzyme and acid production on wheat bran Koji and wheat flour Koji were studied. Asp. niger CF-22 mutant appeared to be tan type which conidial heads were discolored. It's glucoamylase activity was inreased approximately two times and its ${\alpha}-amylase$ about 50 percent as compared with that of the parent strain of Asp. niger CF, when grown on wheat bran Koji under the optimal conditions. Asp. niger CF-21 mutant showed slower growth rate and poor sporulation than the wild type, although its conidial heads were not discolored. Approximately 4-fold increment in its acid production was observed as compared with the weld type. The activities of glucoamylase and ${\alpha}-amylase$ of the Asp. niger CF-22 and CF-21 mutants were higher than those of the wild type, but their protease activity was rather lower. The maximum production of glucoamylase by the Asp. niger CF-22 mutant was obtained after 2 to 3 days incubation on wheat bran at 30 to $35^{\circ}C;$ ${\alpha}-amylase$2 days incubation at 30 to $35^{\circ}C$. The maximal levels of acid production by the mutant CF-21 was appeared after 2 days incubation on wheat bran Koji, and after 3 days on wheat flour Koji at $30^{\circ}C$. Little differences in the levels of acid production were observed between on wheat bran and flour Koji.

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Fragment Analysis for Detection of the FLT3-Internal Tandem Duplication: Comparison with Conventional PCR and Sanger Sequencing (FLT3-ITD 검출을 위한 절편분석법: 일반 중합효소연쇄반응 및 직접염기서열분석법과의 비교)

  • Lee, GunDong;Kim, Jeongeun;Lee, SangYoon;Jang, Woori;Park, Joonhong;Chae, Hyojin;Kim, Myungshin;Kim, Yonggoo
    • Laboratory Medicine Online
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    • v.7 no.1
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    • pp.13-19
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    • 2017
  • Background: We evaluated a sensitive and quantitative method utilizing fragment analysis of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD), simultaneously measuring mutant allele burden and length, and verified the analytical performance. Methods: The number and allelic burden of FLT3-ITD mutations was determined by fragment analysis. Serial mixtures of mutant and wild-type plasmid DNA were used to calculate the limit of detection of fragment analysis, conventional PCR, and Sanger sequencing. Specificity was evaluated using DNA samples derived from 50 normal donors. Results of fragment analysis were compared to those of conventional PCR, using 481 AML specimens. Results: Defined mixtures were consistently and accurately identified by fragment analysis at a 5% relative concentration of mutant to wild-type, and at 10% and 20% ratios by conventional PCR and direct sequencing, respectively. No false positivity was identified. Among 481 AML specimens, 40.1% (193/481) had FLT3-ITD mutations. The mutant allele burden (1.7-94.1%; median, 28.2%) and repeated length of the mutation (14-153 bp; median, 49 bp) were variable. The concordance rate between fragment analysis and conventional PCR was 97.7% (470/481). Fragment analysis was more sensitive than conventional PCR and detected 11 additional cases: seven had mutations below 10%, three cases represented conventional PCR failure, and one case showed false negativity because of short ITD length (14 bp). Conclusions: The new fragment analysis method proved to be sensitive and reliable for the detection and monitoring of FLT3-ITD in patients with AML. This could be used to simultaneously assess ITD mutant allele burden and length.