Targeting Recoding by trans-Translation to Develop Antibiotics.

Abstract

trans-Translation is a recoding event in which a translating ribosome switches from the engaged messenger RNA (mRNA) to a specialized reading frame within transfer-messenger RNA (tmRNA) without releasing the nascent polypeptide, producing a protein that is encoded in two physically distinct RNA molecules. trans-Translation is the most abundant form of recoding and is found throughout the bacterial kingdom. In Escherichia coli growing in liquid culture, ∼5% of newly synthesized proteins are recoded through trans-translation. The importance of this pathway for pathogenic bacteria makes it a potential target for antibiotic development. This review covers the role of trans-translation in pathogenesis, potential points for inhibition, and the progress in developing trans-translation inhibitors as antibiotics.