In most well-studied rod-shaped bacteria, peptidoglycan is primarily crosslinked by penicillin-binding proteins (PBPs). However, in mycobacteria, crosslinks formed by L,D-transpeptidases (LDTs) are highly abundant. To elucidate the role of these unusual crosslinks, we characterized Mycobacterium smegmatis cells lacking all LDTs. We find that crosslinks generate by LDTs 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 spatial and genetic relationship between drug targets can be exploited to more effectively treat this pathogen.
Cite this item
Baranowski, C., Welsh, M. A., Sham, L.-T., Eskandarian, H. A., Lim, H. C., Kieser, K. J., Wagner, J. C., McKinney, J. D., Fantner, G. E., Loerger, T. R., Walker, S., Bernhardt, T. G., Rubin, E. J., & Rego, E. H. (2018). Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape. Elife, 7, Article e37516. https://doi.org/10.7554/eLife.37516
Click Copy to copy the citation, or select the text manually.
WOS:000449729100001
2018-10-16
7
e37516
REVIEWED
EPFL