Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology

Abstract

Ever since the "great oxidation event," Earth's cellular life forms had to cope with the danger of reactive oxygen species (ROS) affecting the integrity of biomolecules and hampering cellular metabolism circuits. Consequently, increasing ROS levels in the biosphere represented growing stress levels and thus shaped the evolution of species. Whether the ROS were produced endogenously or exogenously, different systems evolved to remove the ROS and repair the damage they inflicted. If ROS outweigh the cell's capacity to remove the threat, we speak of oxidative stress. The injuries through oxidative stress in cells are diverse. This article reviews the damage oxidative stress imposes on the different steps of the central dogma of molecular biology in bacteria, focusing in particular on the RNA machines involved in transcription and translation.

Keywords: DNA damage; RNA damage; ROS; oxidative damage; oxidative stress; protein damage.

FIGURE 1

Oxidative stress in bacteria affects every sub step of the central dogma. In bacterial cells the most widely studied reactive oxygen species (ROS) are ¹O₂ (singlet oxygen), O₂ ⁻ (superoxide) and H₂O₂ (hydrogen peroxide), with the latter giving rise to HO• (hydroxyl radicals) via the Fenton reaction (lower left). ROS-dependent oxidations of DNA nucleobases (e.g., 8-oxo-G) or DNA backbone lesions (single-strand breaks; SSB) are recognized and trigger transcriptional responses mediated by oxidative stress-induced transcription factors (e.g., OxyR, PerR, SoxR) (upper left). Bacterial translation is affected in multiple ways by oxidative lesions (red asterisks) as observed in the pool of free amino acids, in elongation factors (EF-Tu, EF-G), ribosomal proteins, and in the main RNA species of the translation machinery (tRNA, rRNA) (upper right and center of the figure). Not necessarily expected, the sub steps of the ribosomal elongation cycle of protein biosynthesis are not affected by ROS to the same extent (center and lower right). While translation initiation and termination do not seem to be markedly inhibited (green check marks), A-site tRNA accommodation, peptide bond formation and EF-G-mediated tRNA translocation are inhibited by oxidative lesions (red cross signs). Please refer to the main text for more details on the ROS-mediated effects on the sub steps of the central dogma.