Research ArticleAntibiotics

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

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Science Translational Medicine  03 Jul 2013:
Vol. 5, Issue 192, pp. 192ra85
DOI: 10.1126/scitranslmed.3006055

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Antibiotics Affect Mitochondria in Mammalian Cells

Antibiotics hurt only bacteria, right? According to a new study from Kalghatgi and colleagues, certain types of antibiotics may also cause damage to mammalian cells and thus pose problems for patients on long-term antibiotic regimens.

The authors hypothesized that bactericidal—but not bacteriostatic—antibiotics damage mammalian tissues by triggering mitochondrial release of reactive oxygen species (ROS). Indeed, in culture, three representative bactericidal antibiotics—ciprofloxacin (a fluoroquinolone), ampicillin (a β-lactam), and kanamycin (an aminoglycoside)—induced dose- and time-dependent increases in intracellular ROS in various human cell lines. Such increases in ROS led to DNA, protein, and lipid damage in vitro. A bacteriostatic antibiotic, tetracycline, had no effect on ROS production. To shed light on the mechanism, Kalghatgi et al. showed that bactericidal antibiotics disrupted the mitochondrial electron transport chain, which would lead to a buildup of ROS.

Mice treated with clinically relevant doses of bactericidal antibiotics similarly showed signs of oxidative damage in blood tests, tissue analysis, and gene expression studies. This ROS-mediated damage could be reversed by the powerful antioxidant N-acetyl-l-cysteine (NAC) without disrupting the bacteria-killing properties of the antibiotics. These studies by Kalghatgi et al. suggest that not only does this damage occur with long-term use of antibiotics, but it can also be prevented by taking antioxidants or by switching to bacteriostatic antibiotics. Nevertheless, it will be important to confirm this antibiotic effect in humans, with a broader range of antibiotics, before any conclusions can be made about oxidative damage to mammalian tissues.

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