Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research.

This paper offers a succinct and compelling summary of some unintended consequences of antibiotic use that goes beyond the usual discussion of emerging resistance and changes in gut flora. Beginning with the well-supported view that tetracycline has the potential to disrupt mitochondrial function, this paper goes on to systematically describe how this activity may compromise experiments in model systems where tetracycline is used as an effector in controlled gene expression systems. The effects of tetracycline on the mitochondrion are likely related to the affinities this organelle has with prokaryotes, with the translational outputs of both being compromised by the antibiotic binding to the 30S ribosomal subunit. The authors go on to document how inhibition of mitochondrial translation by tetracycline leads to a 'mitonuclear protein imbalance' and associated stress responses in a number of widely used eukaryotic animal and plant models, including altered transcription profiles and reduced growth. With respect to tetracycline-controllable gene expression systems used in these models, it is argued that the use of a 'tetracycline only' control may be insufficient to avoid artifactual conclusions, if, for example, changes in transcriptional profiles brought about by non-specific effects on mitochondria sensitise cells to the effects of the target gene under inducible control. Although the primary focus of the paper is the potential shortcomings associated with tetracycline-controlled gene expression systems, the authors conclude with a discussion of how the use of tetracycline in livestock feed has led to its accumulation in some soils at levels sufficient to impact plant growth, and how effects on mitochondria in humans may have relevance in a wide range of diseases.