A fluorescence-based reporter for monitoring expression of mycobacterial cytochrome bd in response to antibacterials and during infection.

Maikel Boot, Kin Ki JIm, T. Liu, S. Commandeur, P. Lu, T. Verboom, H. Lill, W. Bitter, D. Bald

Research output: Contribution to JournalArticleAcademicpeer-review


Cytochrome bd is a component of the oxidative phosphorylation pathway in many Gram-positive and Gram-negative bacteria. Next to its role as a terminal oxidase in the respiratory chain this enzyme plays an important role as a survival factor in the bacterial stress response. In Mycobacterium tuberculosis and related mycobacterial strains, cytochrome bd is an important component of the defense system against antibacterial drugs. In this report we describe and evaluate an mCherry-based fluorescent reporter for detection of cytochrome bd expression in Mycobacterium marinum. Cytochrome bd was induced by mycolic acid biosynthesis inhibitors such as isoniazid and most prominently by drugs targeting oxidative phosphorylation. We observed no induction by inhibitors of protein-, DNA- or RNA-synthesis. The constructed expression reporter was suitable for monitoring mycobacterial cytochrome bd expression during mouse macrophage infection and in a zebrafish embryo infection model when using Mycobacterium marinum. Interestingly, in both these infection models cytochrome bd levels were considerably higher than during in vitro culturing of M. marinum. The expression reporter described here can be a valuable tool for elucidating the role of cytochrome bd as a survival factor.
Original languageEnglish
Article number10665
JournalScientific Reports
Issue number1
Publication statusPublished - 2017


The research leading to these results has received funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution. The grant was awarded to Wilbert Bitter. The authors wish to thank Christina Vandenbroucke-Grauls, Astrid van der Sar for helpful discussions and Anneke Johnson and Henk Hakvoort for technical assistance.

FundersFunder number
Seventh Framework Programme
European Federation of Pharmaceutical Industries and Associations
Innovative Medicines Initiative115337


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