AI Article Synopsis

  • In rod-shaped bacteria, peptidoglycan crosslinking is mainly done by penicillin-binding proteins (PBPs), while mycobacteria rely heavily on L,D-transpeptidases (LDTs) for their unique crosslinks.
  • Research shows that LDTs are essential for maintaining the rod shape of mycobacterial cells, particularly in aging regions of the cell wall due to uneven growth.
  • The absence of LDTs leads to an increased reliance on PBPs for crosslinking, suggesting that combining drugs that inhibit both PBPs and LDTs can enhance the effectiveness of treatments against mycobacteria.

Article 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 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, (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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231781PMC
http://dx.doi.org/10.7554/eLife.37516DOI Listing

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