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RISS 인기검색어
- 검색키워드
- 저자 : Clifton E. Barry (검색결과 13 건)
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조은진,이지임,이명선,김천태,김승철,( Laura E. Via ),( Clifton E. Barry ),조상래,이종석 대한결핵 및 호흡기학회 2013 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.116 No.-
Extensively drug-resistant tuberculosis (XDR-TB) has emerged worldwidely as a threat to public health and TB control. Improper treatment of patients with drug-resistant TB considered as the major cause of increasing XDR-TB cases. Despite of increasing XDR-TB cases, second-line TB drug testings are remained challenging because of international standard methods are not well established and the reproducibility are not good, either. Therefore, for the rapid detection of extensively drug-resistant tuberculosis (XDR-TB), sloppy molecular beacons (SMBs) were designed to detect mutants with resistance to anti-TB drugs such as ofloxacin (OFX) and kanamycin (KM). Resistances to OFX or KM are caused by existence of mutations in a number of genes, including gyrA, gyrB, rrs, and the eis promoter. In this study, mutations were detected by melting temperature (Tm) shifts that occurred when SMBs bind to mismatched sequences. The resulting set of Tm values uniquely identifies the DNA sequences present in the sample. SMB assays were developed for the detection of mutations in rrs and eis promoter, which closely related to the KM resistance in M. tuberculosis. The performance of the SMBs was characterized by studying a total of 560 clinical isolates. The detection and correlation of KM-resistant with phenotypic drug susceptibility test of MGIT960 were examined. The sensitivity and specificity of the assay were 85.1% and 100%, respectively. These results indicate that SMB assay might be the useful means of detecting KM-resistance-associated rrs and eis promoter mutations in M. tuberculosis. Extensively drug-resistant tuberculosis (XDR-TB) has emerged worldwidely as a threat to public health and TB control. Improper treatment of patients with drug-resistant TB considered as the major cause of increasing XDR-TB cases. Despite of increasing XDR-TB cases, second-line TB drug testings are remained challenging because of international standard methods are not well established and the reproducibility are not good, either. Therefore, for the rapid detection of extensively drug-resistant tuberculosis (XDR-TB), sloppy molecular beacons (SMBs) were designed to detect mutants with resistance to anti-TB drugs such as ofloxacin (OFX) and kanamycin (KM). Resistances to OFX or KM are caused by existence of mutations in a number of genes, including gyrA, gyrB, rrs, and the eis promoter. In this study, mutations were detected by melting temperature (Tm) shifts that occurred when SMBs bind to mismatched sequences. The resulting set of Tm values uniquely identifies the DNA sequences present in the sample. SMB assays were developed for the detection of mutations in rrs and eis promoter, which closely related to the KM resistance in M. tuberculosis. The performance of the SMBs was characterized by studying a total of 560 clinical isolates. The detection and correlation of KM-resistant with phenotypic drug susceptibility test of MGIT960 were examined. The sensitivity and specificity of the assay were 85.1% and 100%, respectively. These results indicate that SMB assay might be the useful means of detecting KM-resistance-associated rrs and eis promoter mutations in M. tuberculosis.
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( Eun Sun Son ),( Jiim Lee ),( Derek T. Armstrong ),( Sangnae Cho ),( Laura E. Via ),( Clifton E. Barry ),( Susan E. Dorman ),( Moses L. Joloba ),( Jong Seok Lee ) 대한결핵 및 호흡기학회 2013 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.116 No.-
For Mycobacterium tuberculosis (Mtb), phenotypic methods for drug susceptibility testing (DST) to second-line drugs are poorly standardized and technically challenging. The Sensititreⓡ MYCOTB MIC plate (``MYCOTB``) is a microtitre plate containing lyophilized antibiotics and configured for determination of minimum inhibitory concentrations to first- and second-line anti-tuberculosis drugs. To evaluate performance of MYCOTB for Mtb DST using the Middlebrook 7H10 agar proportion method (APM) as the comparator. We conducted a two-site study using archived Mtb isolates from Uganda and the Republic of Korea. Thawed isolates were subcultured and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, 21; APM results were read at 21 days. 222 isolates provided results on both platforms. Agreement between MYCOTB and APM with respect to ``susceptible`` or ``resistant`` was ≥92% for 7 of 12 drugs when a strict definition was used, and ≥96% for 10 of 12 drugs when agreement was defined allowing for a ± one-well dilution around the APM critical concentration. For ethambutol, agreement was 80-81%. For moxifloxacin, agreement was 83-85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91-96%. For MYCOTB, median time to plate interpretation was 10 days and inter-reader agreement was ≥95% for all drugs. MYCOTB provided reliable results for Mtb DST to first- and second- line drugs except ethambutol, and results were available faster than for APM. For Mycobacterium tuberculosis (Mtb), phenotypic methods for drug susceptibility testing (DST) to second-line drugs are poorly standardized and technically challenging. The Sensititreⓡ MYCOTB MIC plate (``MYCOTB``) is a microtitre plate containing lyophilized antibiotics and configured for determination of minimum inhibitory concentrations to first- and second-line anti-tuberculosis drugs. To evaluate performance of MYCOTB for Mtb DST using the Middlebrook 7H10 agar proportion method (APM) as the comparator. We conducted a two-site study using archived Mtb isolates from Uganda and the Republic of Korea. Thawed isolates were subcultured and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, 21; APM results were read at 21 days. 222 isolates provided results on both platforms. Agreement between MYCOTB and APM with respect to ``susceptible`` or ``resistant`` was ≥92% for 7 of 12 drugs when a strict definition was used, and ≥96% for 10 of 12 drugs when agreement was defined allowing for a ± one-well dilution around the APM critical concentration. For ethambutol, agreement was 80-81%. For moxifloxacin, agreement was 83-85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91-96%. For MYCOTB, median time to plate interpretation was 10 days and inter-reader agreement was ≥95% for all drugs. MYCOTB provided reliable results for Mtb DST to first- and second- line drugs except ethambutol, and results were available faster than for APM.
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( Hongjo Choi ),( Myung Sun Lee ),( Young Ran Kim ),( Clifton E Barry Rd ),( Hae Joo Chung ) 대한결핵 및 호흡기학회 2013 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.116 No.-
Introduction: SES is a well-reported factor associated with tuberculosis morbidity. However, there were no studies to examine the association of SES with treatment adherence of tuberculosis in South Korea. The study aims to investigate an association between SES and treatment adherence. Method: To identify association between SES and treatment adherence, hierarchical logistic regression was performed (Model 1: adjusted for demographic factors; Model 2: Model 1 + individual behavioral factors; Model 3: Model 2 + clinical factors) and treatment regimen-stratified analysis was also conducted. Result: In hierarchical logistic model, poor housing status (adjusted OR: 2.80, 95% CI: 1.27-6.16) and service worker with low education (adjusted OR: 3.33, 95% CI: 1.06-10.43) and laborer group (adjusted OR: 4.39, 95% CI: 1.45-13.28) are significantly associated with the low treatment adherence in Model 3. However, low education is only significantly related to the low treatment adherence in Model 1 (adjusted OR: 1.71, 95% CI: 1.05-2.77). Discussion: The result on this study clearly showed associations of low SES with low treatment adherence in real practice. The study could explain what kind of barriers interferes for TB patients to complete their treatment successfully. This result may be a source to design policy intervention to support TB patients and develop National TB management plan.Introduction: SES is a well-reported factor associated with tuberculosis morbidity. However, there were no studies to examine the association of SES with treatment adherence of tuberculosis in South Korea. The study aims to investigate an association between SES and treatment adherence. Method: To identify association between SES and treatment adherence, hierarchical logistic regression was performed (Model 1: adjusted for demographic factors; Model 2: Model 1 + individual behavioral factors; Model 3: Model 2 + clinical factors) and treatment regimen-stratified analysis was also conducted. Result: In hierarchical logistic model, poor housing status (adjusted OR: 2.80, 95% CI: 1.27-6.16) and service worker with low education (adjusted OR: 3.33, 95% CI: 1.06-10.43) and laborer group (adjusted OR: 4.39, 95% CI: 1.45-13.28) are significantly associated with the low treatment adherence in Model 3. However, low education is only significantly related to the low treatment adherence in Model 1 (adjusted OR: 1.71, 95% CI: 1.05-2.77). Discussion: The result on this study clearly showed associations of low SES with low treatment adherence in real practice. The study could explain what kind of barriers interferes for TB patients to complete their treatment successfully. This result may be a source to design policy intervention to support TB patients and develop National TB management plan.
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Chakravorty, Soumitesh,Lee, Jong Seok,Cho, Eun Jin,Roh, Sandy S.,Smith, Laura E.,Lee, Jiim,Kim, Cheon Tae,Via, Laura E.,Cho, Sang-Nae,Barry III, Clifton E.,Alland, David American Society for Microbiology 2015 Journal of clinical microbiology Vol.53 No.1
<P>Resistance to amikacin (AMK) and kanamycin (KAN) in clinical <I>Mycobacterium tuberculosis</I> strains is largely determined by specific mutations in the <I>rrs</I> gene and <I>eis</I> gene promoter. We developed a rapid, multiplexed sloppy molecular beacon (SMB) assay to identify these mutations and then evaluated assay performance on 603 clinical <I>M. tuberculosis</I> DNA samples collected in South Korea. Assay performance was compared to gold-standard phenotypic drug susceptibility tests, including Lowenstein-Jensen (LJ) absolute concentration, mycobacterial growth indicator tubes (MGIT), and TREK Sensititre MycoTB MIC plate (MycoTB) methods. Target amplicons were also tested for mutations by Sanger sequencing. The SMB assay correctly detected 115/116 mutant and mixed sequences and 487/487 wild-type sequences (sensitivity and specificity of 99.1 and 100%, respectively). Using the LJ method as the reference, sensitivity and specificity for AMK resistance were 92.2% and 100%, respectively, and sensitivity and specificity for KAN resistance were 87.7% and 95.6%, respectively. Mutations in the <I>rrs</I> gene were unequivocally associated with high-level cross-resistance to AMK and KAN in all three conventional drug susceptibility testing methods. However, <I>eis</I> promoter mutations were associated with KAN resistance using the MGIT or MycoTB methods but not the LJ method. No testing method associated <I>eis</I> promoter mutations with AMK resistance. Among the discordant samples with AMK and/or KAN resistance but wild-type sequence at the target genes, we discovered four new mutations in the <I>whiB7</I> 5′ untranslated region (UTR) in 6/22 samples. All six samples were resistant only to KAN, suggesting the possible role of these <I>whiB7</I> 5′ UTR mutations in KAN resistance.</P>
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Woong Park, Sae,Klotzsche, Marcus,Wilson, Daniel J.,Boshoff, Helena I.,Eoh, Hyungjin,Manjunatha, Ujjini,Blumenthal, Antje,Rhee, Kyu,Barry III, Clifton E.,Aldrich, Courtney C.,Ehrt, Sabine,Schnappinger Public Library of Science 2011 PLoS pathogens Vol.7 No.9
<▼1><P>In the search for new drug targets, we evaluated the biotin synthetic pathway of <I>Mycobacterium tuberculosis (Mtb)</I> and constructed an <I>Mtb</I> mutant lacking the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase, BioA. In biotin-free synthetic media, <I>ΔbioA</I> did not produce wild-type levels of biotinylated proteins, and therefore did not grow and lost viability. <I>ΔbioA</I> was also unable to establish infection in mice. Conditionally-regulated knockdown strains of <I>Mtb</I> similarly exhibited impaired bacterial growth and viability <I>in vitro</I> and in mice, irrespective of the timing of transcriptional silencing. Biochemical studies further showed that BioA activity has to be reduced by approximately 99% to prevent growth. These studies thus establish that <I>de novo</I> biotin synthesis is essential for <I>Mtb</I> to establish and maintain a chronic infection in a murine model of TB. Moreover, these studies provide an experimental strategy to systematically rank the <I>in vivo</I> value of potential drug targets in <I>Mtb</I> and other pathogens.</P></▼1><▼2><P><B>Author Summary</B></P><P>We evaluated the biotin synthetic pathway of <I>Mycobacterium tuberculosis</I> (<I>Mtb</I>) as a new drug target by first generating an <I>Mtb</I> deletion mutant, <I>ΔbioA</I>, in which the biotin biosynthetic enzyme 7,8-diaminopelargonic acid synthase (BioA) has been inactivated. This mutant grew in the presence of biotin or <I>des</I>-thiobiotin, but not with an intermediate of the biotin biosynthesis pathway that requires BioA to be converted into biotin. Without exogenous biotin or <I>des</I>-thiobiotin, <I>ΔbioA,</I> was unable to produce biotinylated proteins, which are required for the biosynthesis of fatty acids, and thus died in biotin-free media. Using a regulatable promoter and different ribosome binding sequences we next constructed tightly controlled TetON mutants, in which expression of BioA could be induced with tetracyclines, but was inhibited in their absence. Characterization of these mutants during infections demonstrated that <I>de novo</I> biotin synthesis is not only required to establish infections but also to maintain bacterial persistence. Inhibition of BioA or other enzymes of the biotin biosynthesis pathways could thus be used to kill <I>Mtb</I> during both acute and chronic infections. Biochemical and immunological analyses of different <I>Mtb</I> mutants indicate that drugs targeting BioA would have to inactive approximately 99% of its activity to be effective.</P></▼2>
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환삼덩굴(Humulus japonicus) 추출물의 항결핵 효과
홍민선(Min-Sun Hong),손은순(Eun-Soon Son),이성중(Sung-Joong Lee),이선경(Sun-Kyoung Lee),이예진(Ye-Jin Lee),송선대(Sun-Dae Song),조상래(Sang-Nae Cho),크립톤베리(Clifton E. Barry),엄석용(Seok-Yong Eum) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1
환삼덩굴의 항결핵효능을 알아보기 위하여 두 가지의 실험을 실시하였다. 먼저 환삼덩굴의 메탄올 추출물을 만들어 결핵균에 직접 작용시켰을 때 아주 우수한 결핵균살상효과를 보였다. 두번째로 탐식구에 감염된 결핵균에 대한 증식 억제효능이 있는지 알아 보기 위해 사람의 대식구에 메탄올 추출물을 작용시킨 후 결핵균을 감였시켰을 때 대조군에 비해 현저한 결핵균 증식억제 효과를 보였다. 환삼덩굴의 메탄올 추출물로부터 여러가지 용매를 통해 다섯 가지의 분획물을 얻어 같은 실험을 실시하였다. 이들 분획물 중 결핵균 직접 살상효과를 보인 것은 헥산과 에틸아세테이트층이었고, 탐식구에 감염된 결핵균에 대한 증식억제 효능을 보인 것은 부탄올과 물층이었다. 이처럼 환삼덩굴은 결핵균에 대해 직접적인 살상효과 뿐 아니라 탐식구에 감염되어 있는 결핵균의 증식을 억제하는 효과도 보여 주었는데 이와 같은 결과로 볼 때 환삼덩굴로부터 새로운 결핵치료물질 개발을 기대해 볼 수 있을 것으로 기대된다. The present study aimed to evaluate the in vitro antimycobacterial effects of hop plant, Humulus japonicus. Methanol extract of H. japonicus (MeOH extract) showed strong direct bactericidal effects against Mycobacterium tuberculosis in vitro. Furthermore, the MeOH extract significantly inhibited M. tuberculosis growth in human macrophages. When five fractions obtained from MeOH extract were examined using the same methods, the hexane and ethyl acetate fractions showed bactericidal effects against M. tuberculosis in vitro, whereas the butanol and water fractions inhibited M. tuberculosis growth in macrophages. Because H. japonicus extract exhibited antimycobacterial activity against both free M. tuberculosis in culture medium and intracellular M. tuberculosis in human macrophages, this plant might be a good candidate for development of a new anti-tuberculosis drug.
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