Dataset Information

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

ABSTRACT:

Objectives

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.

Methods

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.

Results

We have shown that fluorescent Mtb can be visualized in the lungs of living mice at a detection limit of ?8?×?10? cfu/lung, whilst in lungs ex vivo a detection limit of ?2?×?10? 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.

Conclusions

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.

SUBMITTER: Zelmer A

PROVIDER: S-EPMC3394442 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Zelmer Andrea A Carroll Paul P Andreu Nuria N Hagens Kristine K Mahlo Jacqueline J Redinger Natalja N Robertson Brian D BD Wiles Siouxsie S Ward Theresa H TH Parish Tanya T Ripoll Jorge J Bancroft Gregory J GJ Schaible Ulrich E UE

The Journal of antimicrobial chemotherapy 20120525 8

<h4>Objectives</h4>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.<h4>Methods</h4>A commercial IVIS Kinetic® system and a custom-built laser scanning system with fluoresce ...[more]

PMID: 22635525

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Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

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