Phosphorylation on PstP controls cell wall metabolism and antibiotic tolerance in Mycobacterium smegmatis [preprint]

12 13 The mycobacterial cell wall is a dynamic structure that protects Mycobacterium 14 tuberculosis and its relatives from environmental stresses. Modulation of cell wall 15 metabolism under stress is thought to be responsible for decreased cell wall permeability 16 and increased tolerance to antibiotics. The signaling pathways that control cell wall 17 metabolism under stress, however, are poorly understood. Here, we examine the 18 signaling capacity of a cell wall master regulator, the Serine Threonine Phosphatase 19 PstP, in the model organism Mycobacterium smegmatis. We studied how interference 20 with a regulatory phosphorylation site on PstP affects growth, cell wall metabolism and 21 antibiotic tolerance. We find that a phospho-mimetic mutation, pstP T171E, slows 22 growth, misregulates both mycolic acid and peptidoglycan metabolism in different 23 conditions, and interferes with antibiotic tolerance. These data suggest that 24 phosphorylation on PstP controls its substrate specificity and is important in the 25 transition between growth and stasis. 26