title: Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria.
abstract: Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein-protein interactions between enzymes with antagonistic functions.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Hett
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chao
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Rubin
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000201:enzymology*; D016207:Cytokines / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D006868:Hydrolysis; D009161:Mycobacterium / Q000201:enzymology*; D046928:Peptidoglycan Glycosyltransferase / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C113704:resuscitation-promoting factor, bacteria; D046928:Peptidoglycan Glycosyltransferase; D010450:Endopeptidases