## 1 Introduction
Secondly, a correct tRNA isoacceptor bound to the respective aaRS repositions its 3'-end into the catalytic active site and a covalent linkage is initially formed at the 2'-OH or 3'-OH of the terminal adenosine of the tRNA with concomitant formation of AMP [8]. Several mechanisms exist to ensure that the correct amino acid gets attached to the end of the tRNA. For this, tRNA forms extensive interactions with the aaRSs using the acceptor stem, the anticodon loop as well as the D and the T\(\psi\)C arm regions [9]. These interactions allow the enzyme to identify recognition elements of different tRNAs, thereby aminoacylating the correct one. Other mechanisms towards maintaining the fidelity of the genetic code involve hydrolysis of the incorrect amino acids after being interrogated by the proofreading mechanisms of the aaRSs [7; 10; 11]. This allows for very low error rates to occur during translation. Once the aminoacylated tRNAs are biosynthesized they rapidly bind to an elongation factor called EF-Tu (elongation factor thermos unstable) and then proceed to the ribosome for protein translation (Figure 1). The bacterial ribosome is a huge 70S ribonucleoprotein complex composed of over 4500 RNA nucleotides and \(\sim\)50 ribosomal proteins. It consists of two subunits denoted as the 50S subunit (large) that contains the peptidyl transferase center and the 30S unit (small) that binds to mRNA and encompasses the decoding center that monitors the tRNA anticodon-codon interaction. The 70S ribosome has three binding sites for the tRNA molecules, which span the space between the two ribosomal subunits: A (aminoacyl), P (peptidyl) and E (exit) sites. In prokaryotes, translation is started by a 30S subunit bound to mRNA forming an initiation complex with the initiation factors IF1, IF2 and IF3 and fMet-tRNAMet that is positioned correctly at the first codon. There is then a coordinated binding event where 50S subunit joins the 30S subunit with release of the initiation factors leaving the codon bound fMet-tRNAMet at the P-site. Incoming EF-Tu-GTP-aa-tRNA complexes then interrogate the mRNA codon at the A-site of the 30S subunit-decoding center with their anticodon stem-loops (Figure 1). Once the correct pairing of codon to anticodon (often involving tRNA modifications) occurs, the GTP bound to EF-Tu is hydrolyzed and releases the aminoacylated tRNA at the A-site. With the correct tRNAs positioned in the P-site and A-site of the ribosome, the peptidyl transferase reaction takes place so as to add the polypeptide chain from the tRNA at the P-site to the tRNA on the A-site (Figure 1). Then, in a reaction catalyzed by an incoming EF-G-GTPase, the A-site tRNA now ligated to the new polypeptide chain translocates along with the mRNA, making it the new P-site and the deacylated tRNA moves over to the E-site to dissociate from the ribosome [12; 13]. The elongation cycle is repeated until a stop codon is encountered leading to the termination stage of translation involving release factors and EF-G, which lead to release of the nascent polypeptide from the ribosome and dissociation of the ribosomal subunits. It is important to note from an antibiotic perspective that although 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]. Thus, 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.