A Small-Molecule Inhibitor of -Translation Synergistically Interacts with Cathelicidin Antimicrobial Peptides To Impair Survival of Staphylococcus aureus.

is a leading cause of infection in the United States, and due to the rapid development of resistance, new antibiotics are constantly needed. -Translation is a particularly promising antibiotic target because it is conserved in many bacterial species, is critical for bacterial survival, and is unique among prokaryotes. We have investigated the potential of KKL-40, a small-molecule inhibitor of -translation, and find that it inhibits both methicillin-susceptible and methicillin-resistant strains of KKL-40 is also effective against Gram-positive pathogens, including a vancomycin-resistant strain of , , and , although its performance with Gram-negative pathogens is mixed.

How a circularized tmRNA moves through the ribosome.

During trans-translation, transfer-messenger RNA (tmRNA) and small protein B (SmpB) together rescue ribosomes stalled on a truncated mRNA and tag the nascent polypeptide for degradation. We used cryo-electron microscopy to determine the structures of three key states of the tmRNA-SmpB-ribosome complex during trans translation at resolutions of 3.7 to 4.

Controlling orthogonal ribosome subunit interactions enables evolution of new function.

Orthogonal ribosomes are unnatural ribosomes that are directed towards orthogonal messenger RNAs in Escherichia coli, through an altered version of the 16S ribosomal RNA of the small subunit. Directed evolution of orthogonal ribosomes has provided access to new ribosomal function, and the evolved orthogonal ribosomes have enabled the encoding of multiple non-canonical amino acids into proteins. The original orthogonal ribosomes shared the pool of 23S ribosomal RNAs, contained in the large subunit, with endogenous ribosomes.