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© 2018, Baranowski et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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.

Details

Title
Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape
Author
Baranowski, Catherine; Welsh, Michael A; Lok-To, Sham; Eskandarian, Haig A; Lim, Hoong C; Kieser, Karen J; Wagner, Jeffrey C; McKinney, John D; Fantner, Georg E; Ioerger Thomas R; Walker, Suzanne; Bernhardt, Thomas G; Rubin, Eric J; Hesper, Rego E
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2018
Publication date
2018
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2140011608
Copyright
© 2018, Baranowski et al. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.