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A new lasso peptide antibiotic exhibits broad-spectrum activity against Gram-negative and Gram-positive bacteria by interfering with bacterial protein synthesis, is unaffected by common resistance mechanisms and shows no toxicity towards human cells.

Single-molecule FRET technologies reveal the mechanism of sequence-specific translational inhibition induced by two antibiotics, chloramphenicol and linezolid, where aminoacyl-tRNA was repeatedly rejected from the A-site and failed to form a peptide bond.

The paenilamicins are hybrid nonribosomal peptide–polyketide compounds that inhibit protein synthesis. Here the authors reveal that paenilamicins bind to a unique site on the ribosome, where they interfere with the translocation of mRNA and tRNAs during elongation.

Hybrids of macrolides and quinolones, called macrolones, can overcome macrolide-induced resistance through new interactions between the quinolone moiety and the ribosome and can concurrently inhibit both ribosome and DNA gyrase targets.

The antimicrobial peptide Drosocin encoded in the fruit fly genome inhibits bacterial translation by stalling the ribosomes at stop codons, sequestering class 1 release factors and inducing stop codon readthrough. Comprehensive mutational analysis reveals key activity determinants of Drosocin.

The authors determine the cryo-EM structures of prokaryotic ribosomes with the oxazolidinone antibiotics linezolid and radezolid bound to the peptidyl transferase center with an adjacent growing nascent peptide chain, providing an explanation for their context-specific action.

High-throughput analysis of translation arrest sites and structural studies reveal tetracenomycin X as a selective protein synthesis inhibitor, acting predominantly at distinct sequence motifs. The drug may be developed as an antibiotic or for treatments based on halting the expression of individual proteins.

Macrolide antibiotics inhibit bacterial translation in a context-specific manner, arresting ribosomes at defined sites within mRNAs and selectively inhibiting synthesis of only a subset of cellular proteins. Here the authors provide a structural basis for the context-specific activity of macrolides on the eukaryotic ribosome.

Bacteria adjust the expression of some of their metabolic enzymes through metabolite-sensing ribosome nascent chain complexes. Here the authors present a cryo-EM structure of an E. coli ribosome stalled during translation of the TnaC leader peptide and propose a model for L-Trp dependent ribosome stalling where L-Trp competes with release factor 2 for binding to the TnaC-ribosome complex.

Ribosome engineering is an emerging powerful approach for synthetic protein synthesis. Here the authors invert the Ribo-T system, using the engineered ribosome to translate the proteome while the native ribosome translates specific mRNA.

The tethered ribosome system Ribo-T supports cell proliferation though at a reduced rate. Here the authors show this is due to slower ribosome assembly instead of reduced functionality.

Ribosomes of all organisms have retained 5S rRNA as an autonomous rRNA species. Here the authors engineer a bacterial strain with ribosomes that do not have free 5S rRNA, and carry structural analyses that suggest the evolutionary preservation of 5S rRNA as an independent molecule is based on its role in the dynamic process of ribosome biogenesis.

Erm methyltransferases confer antimicrobial drug resistance and their expression is induced by macrolides. Gupta et al.show that Erm-catalysed modification of rRNA affects synthesis of some proteins and reduces cell fitness, explaining why expression of Erm is deleterious in the absence of antibiotics.

In bacteria, the ribosomal stalling during translation of leader peptides is a mechanism of antibiotic resistance that has not been well understood. Here, the structure of a drug-dependent stalled ribosome complex has allowed the authors to propose a detailed mechanism for this translational arrest.

Evernimicin, an antibiotic of the orthosomycin class, inhibits bacterial translation by preventing ribosomes from polymerizing specific amino acid motifs, and controls the expression of resistance genes via such context-specific action.

Macrolides and ketolides antibiotics selectively interfere with the translation of a specific subset of proteins. Here the authors show how the macrolide erythromycin and the ketolide telithromycin interplay with the nascent polypeptide chain to arrest translation.

Point mutations in nascent peptides that regulate in the macrolide antibiotic resistance genes ermC and ermB can tune the recognition of the antibiotics erythromycin and telithromycin that control ribosome stalling and gene activation.

Antimicrobial peptide Api137 inhibits translation by trapping release factors 1 or 2 associated with ribosomes and arresting termination.

Here, the authors discuss dual-reporter systems and confounding variables that may lead to misinterpretation of results. They propose guidelines for robust design, physiological interpretation and accurate reporting when using dual reporters.