Regulated proteolysis of a cross-link-specific peptidoglycan hydrolase contributes to bacterial morphogenesis.
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.
Centre for Cellular and Molecular Biology, Hyderabad, India 500007.
Santosh Kumar
SK
Singh
Centre for Cellular and Molecular Biology, Hyderabad, India 500007.
Sadiya
S
Parveen
Centre for Cellular and Molecular Biology, Hyderabad, India 500007.
L
L
SaiSree
Centre for Cellular and Molecular Biology, Hyderabad, India 500007 manjula@ccmb.res.in.
Manjula
M
Reddy
D003432:Cross-Linking Reagents / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development*; D029968:Escherichia coli Proteins / Q000378:metabolism; D009024:Morphogenesis; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism*; D059748:Proteolysis
D003432:Cross-Linking Reagents; D029968:Escherichia coli Proteins; D010457:Peptidoglycan; D009238:N-Acetylmuramoyl-L-alanine Amidase
MepS; NlpI-Prc; bacterial morphogenesis; peptidoglycan; regulated proteolysis