RT Journal Article
SR Electronic
T1 Maturing Mycobacterial Peptidoglycan Requires Non-canonical Crosslinks to Maintain Shape
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 291823
DO 10.1101/291823
A1 Catherine Baranowski
A1 Michael A. Welsh
A1 Lok-To Sham
A1 Haig A. Eskandarian
A1 Hoong C. Lim
A1 Karen J. Kieser
A1 Jeffrey C. Wagner
A1 John D. McKinney
A1 Georg E. Fantner
A1 Thomas R. Ioerger
A1 Suzanne Walker
A1 Thomas G. Bernhardt
A1 Eric J. Rubin
A1 E. Hesper Rego
YR 2018
UL http://biorxiv.org/content/early/2018/04/20/291823.abstract
AB 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.