Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. Through the use of high throughput whole cell screening of an extensive compound library a number of imidazo[1,2-a]pyridine (IP) compounds were obtained as potent lead molecules active against M. tuberculosis and Mycobacterium bovis BCG. The IP inhibitors (1-4) demonstrated minimum inhibitory concentrations (MICs) in the range of 0.03 to 5 mu M against a panel of M. tuberculosis strains. M. bovis BCG spontaneous resistant mutants were generated against IP 1, 3, and 4 at 56 MIC and subsequent whole genome sequencing identified a single nucleotide polymorphism (937)ACC>(937)GCC (T313A) in qcrB, which encodes the b subunit of the electron transport ubiquinol cytochrome C reductase. This mutation also conferred cross-resistance against IP 1, 3 and 4 demonstrating a common target. Gene dosage experiments confirmed M. bovis BCG QcrB as the target where over-expression in M. bovis BCG led to an increase in MIC from 0.5 to >8 mu M for IP 3. An acute murine model of TB infection established bacteriostatic activity of the IP series, which await further detailed characterization.
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[1]
Anaflous A, 2004, LETT DRUG DES DISCOV, V1, P35
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Ananthan, Subramaniam
Faaleolea, Ellen R.
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机构:
So Res Inst, Frederick, MD 21701 USASo Res Inst, Birmingham, AL 35205 USA
Faaleolea, Ellen R.
Goldman, Robert C.
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机构:
NIAID, DHHS, NIH,Therapeut Res Program,Complicat & Coinfect Br, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USASo Res Inst, Birmingham, AL 35205 USA
Goldman, Robert C.
Hobrath, Judith V.
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机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Hobrath, Judith V.
Kwong, Cecil D.
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Kwong, Cecil D.
Laughon, Barbara E.
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h-index: 0
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NIAID, DHHS, NIH,Therapeut Res Program,Complicat & Coinfect Br, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USASo Res Inst, Birmingham, AL 35205 USA
Laughon, Barbara E.
Maddry, Joseph A.
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机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Maddry, Joseph A.
Mehta, Alka
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机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Mehta, Alka
Rasmussen, Lynn
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Rasmussen, Lynn
Reynolds, Robert C.
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机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Reynolds, Robert C.
Secrist, John A., III
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Secrist, John A., III
Shindo, Nice
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Shindo, Nice
Showe, Dustin N.
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So Res Inst, Frederick, MD 21701 USASo Res Inst, Birmingham, AL 35205 USA
Showe, Dustin N.
Sosa, Melinda I.
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Sosa, Melinda I.
Suling, William J.
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Suling, William J.
White, E. Lucile
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
机构:
Int Union TB & Lung Dis, Dept Lung Hlth & NCDs, Paris, FranceFdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
Chiang, Chen-Yuan
Centis, Rosella
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h-index: 0
机构:Fdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
Centis, Rosella
Migliori, Giovanni Battista
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Fdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, ItalyFdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
机构:
Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Christophe, Thierry
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Jackson, Mary
Jeon, Hee Kyoung
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Jeon, Hee Kyoung
Fenistein, Denis
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Fenistein, Denis
Contreras-Dominguez, Monica
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Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Contreras-Dominguez, Monica
Kim, Jaeseung
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kim, Jaeseung
Genovesio, Auguste
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机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Genovesio, Auguste
Carralot, Jean-Philippe
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Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Carralot, Jean-Philippe
Ewann, Fanny
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Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Ewann, Fanny
Kim, Eun Hye
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Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kim, Eun Hye
Lee, Sae Yeon
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机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Lee, Sae Yeon
Kang, Sunhee
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机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kang, Sunhee
Seo, Min Jung
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机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Seo, Min Jung
Park, Eun Jung
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机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Park, Eun Jung
Skovierova, Henrieta
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Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USAInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Skovierova, Henrieta
Pham, Ha
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Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USAInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Pham, Ha
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Riccardi, Giovanna
Nam, Ji Youn
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USA
McGill Univ, Sch Comp Sci, Quebec City, PQ, Canada
McGill Univ, Genome Quebec Innovat Ctr, Quebec City, PQ, CanadaWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Cingolani, Pablo
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Platts, Adrian
Wang, Le Lily
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Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wang, Le Lily
Coon, Melissa
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Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Coon, Melissa
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Tung Nguyen
Wang, Luan
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机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wang, Luan
Land, Susan J.
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Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Land, Susan J.
Lu, Xiangyi
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Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Lu, Xiangyi
Ruden, Douglas M.
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Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Ananthan, Subramaniam
Faaleolea, Ellen R.
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h-index: 0
机构:
So Res Inst, Frederick, MD 21701 USASo Res Inst, Birmingham, AL 35205 USA
Faaleolea, Ellen R.
Goldman, Robert C.
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h-index: 0
机构:
NIAID, DHHS, NIH,Therapeut Res Program,Complicat & Coinfect Br, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USASo Res Inst, Birmingham, AL 35205 USA
Goldman, Robert C.
Hobrath, Judith V.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Hobrath, Judith V.
Kwong, Cecil D.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Kwong, Cecil D.
Laughon, Barbara E.
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h-index: 0
机构:
NIAID, DHHS, NIH,Therapeut Res Program,Complicat & Coinfect Br, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USASo Res Inst, Birmingham, AL 35205 USA
Laughon, Barbara E.
Maddry, Joseph A.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Maddry, Joseph A.
Mehta, Alka
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Mehta, Alka
Rasmussen, Lynn
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Rasmussen, Lynn
Reynolds, Robert C.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Reynolds, Robert C.
Secrist, John A., III
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Secrist, John A., III
Shindo, Nice
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h-index: 0
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So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Shindo, Nice
Showe, Dustin N.
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h-index: 0
机构:
So Res Inst, Frederick, MD 21701 USASo Res Inst, Birmingham, AL 35205 USA
Showe, Dustin N.
Sosa, Melinda I.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Sosa, Melinda I.
Suling, William J.
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
Suling, William J.
White, E. Lucile
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h-index: 0
机构:
So Res Inst, Birmingham, AL 35205 USASo Res Inst, Birmingham, AL 35205 USA
机构:
Int Union TB & Lung Dis, Dept Lung Hlth & NCDs, Paris, FranceFdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
Chiang, Chen-Yuan
Centis, Rosella
论文数: 0引用数: 0
h-index: 0
机构:Fdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
Centis, Rosella
Migliori, Giovanni Battista
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h-index: 0
机构:
Fdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, ItalyFdn S Maugeri, WHO Collaborating Ctr TB & Lung Dis, Care & Res Inst, TBNET Secretariat, I-21049 Tradate, Italy
机构:
Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Christophe, Thierry
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机构:
Jackson, Mary
Jeon, Hee Kyoung
论文数: 0引用数: 0
h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Jeon, Hee Kyoung
Fenistein, Denis
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Fenistein, Denis
Contreras-Dominguez, Monica
论文数: 0引用数: 0
h-index: 0
机构:
Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Contreras-Dominguez, Monica
Kim, Jaeseung
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kim, Jaeseung
Genovesio, Auguste
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Genovesio, Auguste
Carralot, Jean-Philippe
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h-index: 0
机构:
Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Carralot, Jean-Philippe
Ewann, Fanny
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机构:
Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Ewann, Fanny
Kim, Eun Hye
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h-index: 0
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Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kim, Eun Hye
Lee, Sae Yeon
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Lee, Sae Yeon
Kang, Sunhee
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Kang, Sunhee
Seo, Min Jung
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h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Seo, Min Jung
Park, Eun Jung
论文数: 0引用数: 0
h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Park, Eun Jung
Skovierova, Henrieta
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USAInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Skovierova, Henrieta
Pham, Ha
论文数: 0引用数: 0
h-index: 0
机构:
Colorado State Univ, Dept Microbiol Immunol & Pathol, Mycobacteria Res Labs, Ft Collins, CO 80523 USAInst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
Pham, Ha
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机构:
Riccardi, Giovanna
Nam, Ji Youn
论文数: 0引用数: 0
h-index: 0
机构:Inst Pasteur Korea, Biol Intracellular Pathogens Inserm Avenir Grp, Songnam, Gyeonggi Do, South Korea
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USA
McGill Univ, Sch Comp Sci, Quebec City, PQ, Canada
McGill Univ, Genome Quebec Innovat Ctr, Quebec City, PQ, CanadaWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Cingolani, Pablo
论文数: 引用数:
h-index:
机构:
Platts, Adrian
Wang, Le Lily
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wang, Le Lily
Coon, Melissa
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Coon, Melissa
论文数: 引用数:
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机构:
Tung Nguyen
Wang, Luan
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wang, Luan
Land, Susan J.
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Land, Susan J.
Lu, Xiangyi
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Lu, Xiangyi
Ruden, Douglas M.
论文数: 0引用数: 0
h-index: 0
机构:
Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA
Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USAWayne State Univ, Inst Environm Hlth Sci, Detroit, MI 48202 USA