Maturing Mycobacterial Peptidoglycan Requires Non-canonical Crosslinks to Maintain Shape

Autor: Welsh Ma, Thomas R. Ioerger, Catherine Baranowski, Karen J. Kieser, Thomas G. Bernhardt, Hoong Chuin Lim, Lok-To Sham, John D. McKinney, Haig A. Eskandarian, Eric J. Rubin, Rego Eh, Suzanne Walker, Georg E. Fantner, Jeffrey C Wagner
Rok vydání: 2018
Předmět:
DOI: 10.1101/291823
Popis: In 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.
Databáze: OpenAIRE