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 |
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Rok vydání: | 2018 |
Předmět: |
0303 health sciences
Penicillin binding proteins biology 030306 microbiology Cell technology industry and agriculture macromolecular substances biology.organism_classification 3. Good health Mycobacterium tuberculosis 03 medical and health sciences chemistry.chemical_compound medicine.anatomical_structure chemistry Non canonical medicine Biophysics Peptidoglycan Cell aging Pathogen Bacteria 030304 developmental biology |
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 |
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