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Identification of a new family of peptidoglycan transpeptidases reveals atypical crosslinking is essential for viability in Clostridioides difficile
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Identification of a new family of peptidoglycan transpeptidases reveals atypical crosslinking is essential for viability in Clostridioides difficile

Kevin W Bollinger, Ute Müh, Karl L Ocius, Alexis J Apostolos, Marcos M Pires, Richard F Helm, David L Popham, David S Weiss and Craig D Ellermeier
bioRxiv : the preprint server for biology
Cold Spring Harbor Laboratory
03/14/2024
DOI: 10.1101/2024.03.14.584917
PMCID: PMC10980060
PMID: 38559057
url
https://doi.org/10.1101/2024.03.14.584917View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

, the leading cause of antibiotic-associated diarrhea, relies primarily on 3-3 crosslinks created by L,D-transpeptidases (LDTs) to fortify its peptidoglycan (PG) cell wall. This is unusual, as in most bacteria the vast majority of PG crosslinks are 4-3 crosslinks, which are created by penicillin-binding proteins (PBPs). Here we report the unprecedented observation that 3-3 crosslinking is essential for viability in . We also report the discovery of a new family of LDTs that use a VanW domain to catalyze 3-3 crosslinking rather than a YkuD domain as in all previously known LDTs. Bioinformatic analyses indicate VanW domain LDTs are less common than YkuD domain LDTs and are largely restricted to Gram-positive bacteria. Our findings suggest that LDTs might be exploited as targets for antibiotics that kill without disrupting the intestinal microbiota that is important for keeping in check.

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