Investigation of the effects of penicillin-streptomycin antibiotics on mitochondrial DNA copy number

Antibiotics are chemical molecules that have evolved over millions of years as a defense mechanism in microorganisms such as bacteria and fungi. These molecules began to be used in clinical areas with the discovery of their structures and functions. Although antibiotics primarily affect prokaryotic cell organisms, it has been reported that they also have some effects in eukaryotic cells. The effects of the antibiotic Penicillin-Streptomycin (PenStrep), which is frequently used in clinical areas, on eukaryotic cells have not yet been fully elucidated. In a previous study conducted by our team on vitamin D receptors that play a pathological role in Alzheimer's disease (AD), it was shown that the antibiotic PenStrep dose-dependently changed the localization of amyloid beta 1-42 (Aβ1-42) from the cytoplasm to the nucleus in primary cortical neuron cultures. This led us to think that PenStrep application could somehow cause transcriptional changes at the cellular and organelle level by enabling Aβ1-42 to migrate to the nucleus. Considering that Aβ1−42 is also found in organelles such as the endoplasmic reticulum and mitochondria, we thought that PenStrep antibiotics may have an indirect effect on mitochondria and mitochondrial DNA (mtDNA) copy numbers. In the study, the effects of three different doses of PenStrep antibiotic application on mtDNA copy numbers in HEK293T cells were investigated. As a result, it was observed that mtDNA copy numbers increased statistically significantly in the groups that were applied 5 and 15 IU for 24 hours and 10 IU for 48 hours compared to the control groups. This increase in mtDNA copy numbers observed with low-dose antibiotic application may be a compensation mechanism aimed at maintaining the activity of the oxidative phosphorylation system. The situation observed at high doses may be related to the cell producing more mitochondria in the face of high oxidative stress. The increase observed in 10 IU PenStrep application for 48 hours can be explained by the fact that oxidative stress occurring at this dose in the cell only manifests itself during this period. More detailed and comprehensive studies are needed to establish the relationship between the increase in mtDNA copy number with antibiotic application and cellular and molecular mechanisms. Understanding the physiological effects of PenStrep antibiotic on mitochondria is important to understand the participation of antibiotics in pathological mechanisms. Keywords: penicillin, streptomycin, antibiotic, mitochondria, DNA