A new in vivo model to test anti-tuberculosis drugs using fluorescence imaging

被引：62

作者：

Zelmer, Andrea ^{[1
]}

Carroll, Paul ^{[2
]}

Andreu, Nuria ^{[3
]}

Hagens, Kristine ^{[4
]}

Mahlo, Jacqueline ^{[4
]}

Redinger, Natalja ^{[4
]}

Robertson, Brian D. ^{[3
]}

Wiles, Siouxsie ^{[5
,6
]}

Ward, Theresa H. ^{[1
]}

Parish, Tanya ^{[2
,8
]}

Ripoll, Jorge ^{[7
]}

Bancroft, Gregory J. ^{[1
]}

Schaible, Ulrich E. ^{[1
,4
]}

机构：

[1] Univ London London Sch Hyg & Trop Med, Immunol & Infect Dept, Fac Infect & Trop Dis, London WC1E 7HT, England

[2] Queen Mary Univ London, Ctr Immunol & Infect Dis, Barts & London Sch Med & Dent, London E1 2AT, England

[3] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England

[4] Res Ctr Borstel, Dept Mol Infect Res, D-23845 Borstel, Germany

[5] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W12 0NN, England

[6] Univ Auckland, Dept Mol Med & Pathol, Auckland 1142, New Zealand

[7] Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece

[8] Infect Dis Res Inst, Seattle, WA 98104 USA

来源：

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | 2012年 / 67卷 / 08期

关键词：

antibiotics; drug testing; mycobacteria; optical imaging; TB; STERILIZING ACTIVITY; MURINE MODEL; TUBERCULOSIS; RED; MOUSE; GENE; MOXIFLOXACIN; DYNAMICS; REGIMENS; EFFICACY;

D O I：

10.1093/jac/dks161

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

The current method for testing new drugs against tuberculosis in vivo is the enumeration of bacteria in organs by cfu assay. Owing to the slow growth rate of Mycobacterium tuberculosis (Mtb), these assays can take months to complete. Our aim was to develop a more efficient, fluorescence-based imaging assay to test new antibiotics in a mouse model using Mtb reporter strains. A commercial IVIS Kinetic system and a custom-built laser scanning system with fluorescence molecular tomography (FMT) capability were used to detect fluorescent Mtb in living mice and lungs ex vivo. The resulting images were analysed and the fluorescence was correlated with data from cfu assays. We have shown that fluorescent Mtb can be visualized in the lungs of living mice at a detection limit of approximate to 810(7) cfu/lung, whilst in lungs ex vivo a detection limit of approximate to 210(5) cfu/lung was found. These numbers were comparable between the two imaging systems. Ex vivo lung fluorescence correlated to numbers of bacteria in tissue, and the effect of treatment of mice with the antibiotic moxifloxacin could be visualized and quantified after only 9 days through fluorescence measurements, and was confirmed by cfu assays. We have developed a new and efficient method for anti-tuberculosis drug testing in vivo, based on fluorescent Mtb reporter strains. Using this method instead of, or together with, cfu assays will reduce the time required to assess the preclinical efficacy of new drugs in animal models and enhance the progress of these candidates into clinical trials against human tuberculosis.

引用

页码：1948 / 1960

页数：13

共 39 条

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