Oliveira Paiva Ana M, Courtin Pascal, Charpentier Glenn, Oueled-Chama Imane, Soutourina Olga, Chapot-Chartier Marie-Pierre, Peltier Johann
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Gif-sur-Yvette, France.
Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France.
iScience. 2025 Mar 16;28(4):112227. doi: 10.1016/j.isci.2025.112227. eCollection 2025 Apr 18.
The resistance of to the β-lactam antibiotics cephalosporins, which target the peptidoglycan (PG) assembly, is a leading contributor to the development of infections. has an original PG structure with a predominance of 3→3 cross-links generated by l,d-transpeptidases (LDTs). forms spores and we show that the spore cortex PG contains exclusively 3→3 cross-links. PG and spore cortex of 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 .
对靶向肽聚糖（PG）组装的β-内酰胺类抗生素头孢菌素的耐药性是导致感染发生的主要因素。具有独特的PG结构，主要由l，d-转肽酶（LDTs）产生3→3交联。形成孢子，我们发现孢子皮层PG仅含有3→3交联。细胞的PG和孢子皮层在很大程度上不受三种预测的LDTs缺失的影响，这揭示了一个新的LDTs家族的作用。产生必需LDT底物的d，d-羧肽酶被头孢菌素灭活，导致l，d-转肽途径受到抑制。相反，在抗生素存在的情况下，青霉素结合蛋白（PBPs）对PG交联的参与增加。我们的研究结果突出表明，头孢菌素耐药性并非主要由LDTs介导，并说明了PG生物合成机制在中的可塑性。
