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.
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
