Maturing Mycobacterial Peptidoglycan Required Non-canonical Crosslinks to Maintain Shape Institutional Repository Document uri icon


  • AbstractIn most well studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin binding proteins (PBPs). However, in mycobacteria, L,D-transpeptidase (LDT)-mediated crosslinks are highly abundant. To elucidate the role of these unusual crosslinks, we characterized mycobacterial cells lacking all LDTs. We find that LDT-mediated crosslinks are required for rod shape maintenance specifically at sites of aging cell wall, a byproduct of polar elongation. Asymmetric polar growth leads to a non-uniform distribution of these two types of crosslinks in a single cell. Consequently, in the absence of LDT-mediated crosslinks, PBP-catalyzed crosslinks become more important. Because of this,Mycobacterium tuberculosis(Mtb) is more rapidly killed using a combination of drugs capable of PBP- and LDT-inhibition. Thus, knowledge about the single-cell distribution of drug targets can be exploited to more effectively treat this pathogen.

altmetric score

  • 18.1

author list (cited authors)

  • Baranowski, C., Sham, L., Eskandarian, H. A., Welsh, M. A., Lim, H. C., Kieser, K. J., ... Rego, E. H.

citation count

  • 3

complete list of authors

  • Baranowski, Catherine||Sham, Lok-To||Eskandarian, Haig A||Welsh, Michael A||Lim, Hoong C||Kieser, Karen J||Wagner, Jeffrey C||Walker, Suzanne||McKinney, John D||Fantner, Georg E||Ioerger, Thomas R||Bernhardt, Thomas G||Rubin, Eric J||Rego, E Hesper

Book Title

  • bioRxiv

publication date

  • March 2018