The l,d-transpeptidation pathway is inhibited by antibiotics of the β-lactam class in <i>Clostridioides difficile</i>.

ABSTRACT: The resistance of Clostridioides difficile to the β-lactam antibiotics cephalosporins, which target the peptidoglycan (PG) assembly, is a leading contributor to the development of C. difficile infections. C. difficile has an original PG structure with a predominance of 3→3 cross-links generated by l,d-transpeptidases (LDTs). C. difficile forms spores and we show that the spore cortex PG contains exclusively 3→3 cross-links. PG and spore cortex of C. difficile cells were largely unaffected by the deletion of the three predicted LDTs, revealing the implication of a new family of LDTs. The d,d-carboxypeptidases producing the essential LDT substrate were inactivated by cephalosporins, resulting in the inhibition of the l,d-transpeptidation pathway. In contras

SUBMITTER: Oliveira Paiva AM 

PROVIDER: S-EPMC11986978 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature