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Bacterial intracellular DNA and RNA are the fundamental molecules responsible for the storage, transmission, and expression of genetic information in prokaryotes. The bacterial genome typically consists of a single circular double-stranded DNA molecule, while the transcriptome includes various RNA species such as messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These nucleic acids are essential for bacterial survival, as they serve as templates for replication and the synthesis of proteins via the 70S ribosome. In clinical pharmacology, these molecules are targeted by several classes of antimicrobial agents that either damage the DNA structure or bind to ribosomal RNA to disrupt translation. For example, metronidazole induces DNA strand breaks through the formation of reactive intermediates, while aminoglycosides and macrolides bind to the 16S and 23S rRNA subunits, respectively [1, 2, 3]. Because these targets are ubiquitous across bacterial species but differ structurally from eukaryotic counterparts, they provide a broad spectrum of activity for treating infections [5]. However, the high degree of conservation in these targets also means that mutations can lead to widespread antibiotic resistance, and the similarity between bacterial and human mitochondrial ribosomes can lead to off-target toxicities [2, 4].
Drugs targeting bacterial nucleic acids function through several distinct mechanisms: nitroimidazoles and nitrofuran derivatives undergo intracellular reduction to form reactive radicals that cause direct oxidative damage and strand breakage of bacterial DNA [1, 4]; aminoglycosides bind to the A-site of the 16S ribosomal RNA (rRNA) to induce mRNA misreading and inhibit translocation [2, 5]; and macrolides, lincosamides, and oxazolidinones bind to the 23S rRNA of the 50S ribosomal subunit to block peptidyl transferase activity or prevent the exit of nascent peptide chains [2, 3].
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