Induction and regulation of a secreted peptidoglycan hydrolase by a membrane Ser/Thr kinase that detects muropeptides.
Here, we report that the model Gram-positive organism, Bacillus subtilis, expresses and secretes a muralytic enzyme, YocH, in response to cell wall-derived muropeptides derived from growing cells but not lysed cells. This induction is dependent on PrkC, a membrane Ser/Thr kinase that binds to peptidoglycan and that belongs to a broadly conserved family including the essential PknB kinase of M. tuberculosis. YocH stimulates its own expression in a PrkC-dependent manner demonstrating the presence of an autoregulatory loop during growth. Cells lacking YocH display a survival defect in stationary phase but enzymes secreted by other cells in the culture rescue this defect. The essential translation factor EF-G is an in vivo substrate of PrkC and this phosphorylation occurs in response to muropeptides. Therefore, we hypothesize that YocH is used by the bacterium to digest peptidoglycan released by other bacteria in the milieu and that the presence of these fragments is detected by a membrane kinase that modifies a key regulator of translation as well as to stimulate its own expression.
Shah
Ishita M
IM
Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Dworkin
Jonathan
J
D001412:Bacillus subtilis / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D008954:Models, Biological; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D001426:Bacterial Proteins; D010455:Peptides; D010457:Peptidoglycan; D017346:Protein Serine-Threonine Kinases; D009238:N-Acetylmuramoyl-L-alanine Amidase