Microcins reveal natural mechanisms of bacterial manipulation to inform therapeutic development.

Microcins are an understudied and poorly characterized class of antimicrobial peptides. Despite the existence of only 15 examples, all identified from the Enterobacteriaceae, microcins display diversity in sequence, structure, target cell uptake, cytotoxic mechanism of action and target specificity. Collectively, these features describe some of the unique means nature has contrived for molecules to cross the 'impermeable' barrier of the Gram-negative bacterial outer membrane and inflict cytotoxic effects. Microcins appear to be widely dispersed among different species and in different environments, where they function in regulating microbial communities in diverse ways, including through competition. Growing evidence suggests that microcins may be adapted for therapeutic uses such as antimicrobial drugs, microbiome modulators or facilitators of peptide uptake into cells. Advancing our biological, ecological and biochemical understanding of the roles of microcins in bacterial interactions, and learning how to regulate and modify microcin activity, is essential to enable such therapeutic applications.

Conserved bacterial RNase YbeY plays key roles in 70S ribosome quality control and 16S rRNA maturation.

Quality control of ribosomes is critical for cellular function since protein mistranslation leads to severe physiological consequences. We report evidence of a previously unrecognized ribosome quality control system in bacteria that operates at the level of 70S to remove defective ribosomes. YbeY, a previously unidentified endoribonuclease, and the exonuclease RNase R act together by a process mediated specifically by the 30S ribosomal subunit, to degrade defective 70S ribosomes but not properly matured 70S ribosomes or individual subunits. Furthermore, there is essentially no fully matured 16S rRNA in a ΔybeY mutant at 45°C, making YbeY the only endoribonuclease to be implicated in the critically important processing of the 16S rRNA 3' terminus. These key roles in ribosome quality control and maturation indicate why YbeY is a member of the minimal bacterial gene set and suggest that it could be a potential target for antibacterial drugs.