Open Access Highly Accessed Research article

Regulation of Polar Peptidoglycan Biosynthesis by Wag31 Phosphorylation in Mycobacteria

Charul Jani1, Hyungjin Eoh2, Jae Jin Lee4, Khozima Hamasha3, Moodakare Bheema Sahana3, Jeong-Sun Han4, Seeta Nyayapathy1, Jung-Yeon Lee4, Joo-Won Suh4, Sang Hee Lee4, Steve J Rehse3, Dean C Crick2 and Choong-Min Kang1*

Author Affiliations

1 Department of Biological Science, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA

2 Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery Ft. Collins, CO 80523, USA

3 Department of Physics & Astronomy, Wayne State University, Detroit, MI 48201, USA

4 Department of Biological Sciences, Myongji University, San 38-2 Namdong, Yongin, Gyeonggido, 449-728, Republic of Korea

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BMC Microbiology 2010, 10:327  doi:10.1186/1471-2180-10-327

Published: 29 December 2010



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.


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.


The Wag31Mtb phosphorylation is a novel molecular mechanism by which Wag31Mtb regulates peptidoglycan synthesis and thus, optimal growth in mycobacteria.