title: Regulation of polar peptidoglycan biosynthesis by Wag31 phosphorylation in mycobacteria.
abstract: BACKGROUND
  Sensing and responding to environmental changes is a central aspect of cell division regulation. Mycobacterium tuberculosis contains eleven Ser/Thr kinases, two of which, PknA and PknB, are key signaling molecules that regulate cell division/morphology. One substrate of these kinases is Wag31, and we previously showed that partial depletion of Wag31 caused morphological changes indicative of cell wall defects, and that the phosphorylation state of Wag31 affected cell growth in mycobacteria. In the present study, we further characterized the role of the Wag31 phosphorylation in polar peptidoglycan biosynthesis.
  
  
  RESULTS
  We demonstrate that the differential growth among cells expressing different wag31 alleles (wild-type, phosphoablative, or phosphomimetic) is caused by, at least in part, dissimilar nascent peptidoglycan biosynthesis. The phosphorylation state of Wag31 is found to be important for protein-protein interactions between the Wag31 molecules, and thus, for its polar localization. Consistent with these results, cells expressing a phosphomimetic wag31 allele have a higher enzymatic activity in the peptidoglycan biosynthetic pathway.
  
  
  CONCLUSIONS
  The Wag31Mtb phosphorylation is a novel molecular mechanism by which Wag31Mtb regulates peptidoglycan synthesis and thus, optimal growth in mycobacteria.
authors.affiliation: Department of Biological Science, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
authors.forename: Charul
authors.initials: C
authors.lastname: Jani
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Eoh
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Khozima
authors.initials: K
authors.lastname: Hamasha
authors.forename: Moodakare Bheema
authors.initials: MB
authors.lastname: Sahana
authors.forename: Jeong-Sun
authors.initials: JS
authors.lastname: Han
authors.forename: Seeta
authors.initials: S
authors.lastname: Nyayapathy
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
authors.forename: Sang Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Rehse
authors.forename: Dean C
authors.initials: DC
authors.lastname: Crick
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Kang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D020102:Mycobacterium smegmatis / Q000737:chemistry / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D010457:Peptidoglycan / Q000096:biosynthesis* / Q000737:chemistry; D010766:Phosphorylation; D021381:Protein Transport
chemical_list: D001426:Bacterial Proteins; D010457:Peptidoglycan