Mitochondria, the Missing Microbe: Tetracycline Reduces Mitochondria Copy Number to Promote Antibiotic Induced Triglyceride Accumulation

Abstract

Across biological organisms, antibiotics are known to promote triglyceride accumulation, and microbiome composition changes in response to antibiotics have received sole attention while potential host (non-microbiome) targets have been ignored. Of these host targets, mitochondria are of particular interest, so I measured triglyceride levels, the production of reactive oxygen species (ROS), and variation in mitochondria copy number in isogenic Drosophila melanogaster with and without a microbiome treated with low doses of tetracycline. Tetracycline treatment in Drosophila with a normal microbiome increased triglyceride levels while reducing mitochondria copy number but has no significant effect on ROS production. In order to determine if tetracycline promotes triglyceride accumulation independently from the microbiome, axenic Drosophila also underwent tetracycline treatment. Axenic Drosophila showed increased triglyceride accumulation, no changes in ROS production, and possible reductions in mitochondria copy number that need further investigation. From these results, I conclude that tetracycline likely directly affects the host to promote triglyceride accumulation independently from the microbiome, and reduction in mitochondria copy number is the likely host target responsible for this phenomenon. Reductions in mitochondria copy number likely work in concert with microbiome composition changes to produce the triglyceride accumulation phenotype in response to tetracycline.