Abstract
Transfer RNAs (tRNAs) are central players in the protein translation machinery and as such are prominent targets for a large number of natural and synthetic antibiotics. This review focuses on the role of tRNAs in bacterial antibiosis. We will discuss examples of antibiotics that target multiple stages in tRNA biology from tRNA biogenesis and modification, mature tRNAs, aminoacylation of tRNA as well as prevention of proper tRNA function by small molecules binding to the ribosome. Finally, the role of deacylated tRNAs in the bacterial “stringent response” mechanism that can lead to bacteria displaying antibiotic persistence phenotypes will be discussed.
Highlights
TRNAs are the key decoding adaptors in the protein synthesis machinery that allows the mRNA genetic code to be translated into a linear sequence of amino acids in a polypeptide chain [1,2]
Genes that are essential is an important feature of targeting novel broad spectrum antibiotics, this does not exclude the possibility that some Transfer RNAs (tRNAs) modifications maybe required to support pathogenic lifestyles of certain bacteria and could be targets for more selective antimicrobials
We have highlighted that antibiotics can target a significant number of key processing and tailoring steps that are essential for tRNAs to carry out their role in translation
Summary
TRNAs are the key decoding adaptors in the protein synthesis machinery that allows the mRNA genetic code to be translated into a linear sequence of amino acids in a polypeptide chain [1,2]. There are numerous tRNA isoacceptors for each of the canonical 20 amino acids designated by the genetic code [3] These tRNA species show a significant variety in both base sequence and modifications in both prokaryotes and eukaryotes while still maintaining the ability to bind to the highly conserved ribosome active sites [4]. It is important to note from an antibiotic perspective that the eukaryotic protein translation machinery works in similar manner to the prokaryotic one, there are significant differences, such as ribosomes size (80S in the case of eukaryotes), differences in ribosomal proteins and translation factors and variation in tRNA number, sequence and modifications [14] All these processes where tRNAs are involved can be targets for new drugs. In the sections described below, we aim to summarize the mechanisms of known antibiotics that target tRNAs involved in different processes
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