• Abstract Antimicrobial drug resistance poses a global health challenge that necessitates the identification of new druggable targets1,2,3 • The essential lipid II flippase MurJ is a promising yet underexplored antimicrobial target in bacterial cell wall biosynthesis4,5,6,7 • The only known inhibitors of Gram-negative (diderm) MurJ are the single-gene lysis proteins (Sgls) from the lytic single-strand RNA phages M (SglM) and PP7 (SglPP7)8,9 • SglM and SglPP7 have distinct evolutionary origins and share no sequence similarity • Here we describe a common mechanism of MurJ inhibition by these phage-encoded Sgls • We determined the structures of MurJ-bound SglM and SglPP7 and discovered a third distinct MurJ-targeting Sgl from the predicted phage Changjiang3 (SglCJ3) that we also characterized structurally

Article Summaries:

  • Abstract Antimicrobial drug resistance poses a global health challenge that necessitates the identification of new druggable targets1,2,3. The essential lipid II flippase MurJ is a promising yet underexplored antimicrobial target in bacterial cell wall biosynthesis4,5,6,7. The only known inhibitors of Gram-negative (diderm) MurJ are the single-gene lysis proteins (Sgls) from the lytic single-strand RNA phages M (SglM) and PP7 (SglPP7)8,9. SglM and SglPP7 have distinct evolutionary origins and share no sequence similarity. Here we describe a common mechanism of MurJ inhibition by these phage-en

Sources: