title: Wag31, a homologue of the cell division protein DivIVA, regulates growth, morphology and polar cell wall synthesis in mycobacteria.
abstract: The Mycobacterium tuberculosis genome contains 11 serine/threonine kinase genes, and the products of two of these, PknA and PknB, are key components of a signal transduction pathway that regulates cell division and/or morphology. Previously, we have shown that one substrate of these kinases is Wag31, a homologue of the cell division protein DivIVA that is present, but not known to be phosphorylated, in other Gram-positive bacteria. Here, we investigate the localization and function of Wag31 and its phosphorylation. We demonstrate that Wag31 is localized to the cell poles. We further show that wag31 is an essential gene and that depletion of its product causes a dramatic morphological change in which one end of the cell becomes round rather than rod-shaped. This abnormal morphology appears to be caused by a defect in polar peptidoglycan synthesis. Finally, expression of M. tuberculosis wag31 in the wag31 conditional mutant of Mycobacterium smegmatis altered the growth rate in a manner that depended on the phospho-acceptor residue encoded by the allele being expressed. Taken together, these results indicate that Wag31 regulates cell shape and cell wall synthesis in M. tuberculosis through a molecular mechanism by which the activity of Wag31 can be modulated in response to environmental signals.
authors.affiliation: Department of Biological Science, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Kang
authors.affiliation: Department of Biological Science, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA.
authors.forename: Seeta
authors.initials: S
authors.lastname: Nyayapathy
authors.affiliation: Department of Biological Science, Myongji University, San 38-2, Namdong, Yongin, Republic of Korea.
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Myongji University, San 38-2, Namdong, Yongin, Republic of Korea.
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Suh
authors.affiliation: Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave., Boston, MA 02115, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Husson
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002473:Cell Wall / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020043:Genes, Essential; D005816:Genetic Complementation Test; D020102:Mycobacterium smegmatis / Q000737:chemistry / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000235:genetics; D010457:Peptidoglycan / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; C104636:DivIVA protein, bacteria; D010457:Peptidoglycan