The L,D-transpeptidation pathway is inhibited by antibiotics of the β-lactam class in Clostridioides difficile
2025
Paiva, Ana, M Oliveira | Courtin, Pascal | Charpentier, Glenn | Soutourina, Olga | Chapot-Chartier, Marie-Pierre | Peltier, Johann | Institut de Biologie Intégrative de la Cellule (I2BC) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | ANR-11-EQPX-0029,MORPHOSCOPE 2,Imagerie et reconstruction multiéchelles de la morphogenèse. (Plateforme d'innovation technologique et méthodologique pour l'imagerie in vivo et la reconstruction des dynamiques multiéchelles de la morphogenèse)(2011) | ANR-20-CE15-0003,DIFFICROSS,Génération des ponts interpeptidiques du peptidoglycane par des L,D-transpeptidases chez Clostridioides difficile: rôle dans la résistance aux antibiotiques et la libération des toxines(2020)
Summary 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 contrast, the participation of penicillin-binding proteins (PBPs) to PG cross-linking increased in the presence of the antibiotics. Our findings highlight that cephalosporin resistance is not primarily mediated by LDTs and illustrate the plasticity of the PG biosynthesis machinery in C. difficile .
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
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