Antibiotic use and abuse: a threat to mitochondria and chloroplasts with impact on research, health, and environment

Abstract

Recently, several studies have demonstrated that tetracyclines, the antibiotics most intensively used in livestock and that are also widely applied in biomedical research, interrupt mitochondrial proteostasis and physiology in animals ranging from round worms, fruit flies, and mice to human cell lines. Importantly, plant chloroplasts, like their mitochondria, are also under certain conditions vulnerable to these and other antibiotics that are leached into our environment. Together these endosymbiotic organelles are not only essential for cellular and organismal homeostasis stricto sensu, but also have an important role to play in the sustainability of our ecosystem as they maintain the delicate balance between autotrophs and heterotrophs, which fix and utilize energy, respectively. Therefore, stricter policies on antibiotic usage are absolutely required as their use in research confounds experimental outcomes, and their uncontrolled applications in medicine and agriculture pose a significant threat to a balanced ecosystem and the well-being of these endosymbionts that are essential to sustain health.

Keywords: antibiotics; chloroplasts; doxycycline; environmental pollution; mitochondria; mitochondrial unfolded protein response; tetracycline.

Figure 1

Conceptual figure illustrating the general idea showing the targeted effect of antibiotics. A: Antibiotics induce bacterial cell death meanwhile also interrupting the function of endosymbiotic organelles, mitochondria, and chloroplast, and generating a signal turning on the unfolded protein response pathways in eukaryotic cells. B: A schematic figure showing the targeted effect of tetracyclines on the Tet‐On/Tet‐Off system in nucleus and their adverse collateral effects on mitochondrial translation. Other antibiotics, such as the amphenicols, also have similar effects on the mitochondria. Using antibiotics that impair mitochondrial translation can induce a mitonuclear protein imbalance and lead to the mitochondrial unfolded protein response (UPR^mt) pathway.

Figure 2

Usages of antibiotics in China, USA, and EU. A: Uses of antibiotics in human medicine, animals, and crop production. Data are from sales figures, which may not exactly reflect consumption. Usage data in crops in China were estimated from validamycin use, which consists of the majority of antibiotics consumption in China. A zoomed‐in chart shows antibiotics usage for crop production in the USA, which can hardly be seen in the main graph. Application of antibiotics in crop production is banned in the EU. B: Antibiotics most frequently used in humans and animals. The data on the antibiotics used in China are selected from those antibiotics that are frequently detected in the environment. Some antibiotics with relatively high use are not included due to their low detection frequencies 38. Although not in the top, a substantial amount of tetracyclines were sold in China, as indicated.

Figure 3

Sources and pathways of how antibiotics are released into the environment. Antibiotics reach the environment through multiple ways, the main pathways beginning from human and agricultural use are highlighted. The thickness of the arrows reflects the relative importance of the pathways.

Figure 4

Schematic diagram of the impact of antibiotics on a hypothetical plant cell. For simplicity, all factors are presented in the same plant cell. Arrows indicate positive regulations and bars mean negative regulations. ROS, reactive oxygen species; MDA, malondialdehyde, is an end product of lipid peroxidation.