Regulated proteolysis of a cross-link-specific peptidoglycan hydrolase contributes to bacterial morphogenesis

Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):10956-61. doi: 10.1073/pnas.1507760112. Epub 2015 Aug 17.

Abstract

Bacterial growth and morphogenesis are intimately coupled to expansion of peptidoglycan (PG), an extensively cross-linked macromolecule that forms a protective mesh-like sacculus around the cytoplasmic membrane. Growth of the PG sacculus is a dynamic event requiring the concerted action of hydrolases that cleave the cross-links for insertion of new material and synthases that catalyze cross-link formation; however, the factors that regulate PG expansion during bacterial growth are poorly understood. Here, we show that the PG hydrolase MepS (formerly Spr), which is specific to cleavage of cross-links during PG expansion in Escherichia coli, is modulated by proteolysis. Using combined genetic, molecular, and biochemical approaches, we demonstrate that MepS is rapidly degraded by a proteolytic system comprising an outer membrane lipoprotein of unknown function, NlpI, and a periplasmic protease, Prc (or Tsp). In summary, our results indicate that the NlpI-Prc system contributes to growth and enlargement of the PG sacculus by modulating the cellular levels of the cross-link-cleaving hydrolase MepS. Overall, this study signifies the importance of PG cross-link cleavage and its regulation in bacterial cell wall biogenesis.

Keywords: MepS; NlpI-Prc; bacterial morphogenesis; peptidoglycan; regulated proteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / metabolism
  • Escherichia coli / growth & development*
  • Escherichia coli Proteins / metabolism
  • Morphogenesis*
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism*
  • Peptidoglycan / metabolism*
  • Proteolysis

Substances

  • Cross-Linking Reagents
  • Escherichia coli Proteins
  • Peptidoglycan
  • N-Acetylmuramoyl-L-alanine Amidase