N-Deacetylases required for muramic-δ-lactam production are involved in Clostridium difficile sporulation, germination, and heat resistance - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Journal of Biological Chemistry Year : 2018

N-Deacetylases required for muramic-δ-lactam production are involved in Clostridium difficile sporulation, germination, and heat resistance

Aline Rifflet
  • Function : Author
Richard Wheeler
  • Function : Author
Ivo Gomperts Boneca
  • Function : Author
Thomas Candela

Abstract

Spores are produced by many organisms as the result of a survival mechanism, triggered under several environmental stresses. These are multi-layered structures, one of which is a peptidoglycan layer known as the cortex. This structure contains muramic-δ-lactams that are synthesized by at least two enzymes, CwlD and PdaA. This study focuses on the spore cortex of Clostridium difficile, a Gram-positive spore-forming, toxin-producing anaerobic pathogen that can colonize the intestinal tract of humans, considered as the leading cause of antibiotic-associated diarrhea. The cortex of the C. difficile 630∆erm strain was analyzed using UHPLC coupled to HRMS. This analysis revealed that C. difficile cortex differs from B. subtilis cortex. Amongst these differences, the muramic-δ-lactams represented 24% in C. difficile, compared to 50% in B. subtilis. CD630_14300 and CD630_27190 were identified as the genes encoding the C. difficile N-deacetylases PdaA1 and PdaA2, responsible for muramic-δ-lactam synthesis. In the pdaA1 mutant only 0.4% of all muropeptides carry a muramic-δ-lactam modification, and no muramic-δ-lactam were found in the cortex of the double mutant pdaA1-pdaA2. Surprisingly, our results suggest a much broader impact for muramic-δ-lactams in C. difficile compared to previously characterized model organisms, such
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hal-04374612 , version 1 (05-01-2024)

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Héloise Coullon, Aline Rifflet, Richard Wheeler, Claire Janoir, Ivo Gomperts Boneca, et al.. N-Deacetylases required for muramic-δ-lactam production are involved in Clostridium difficile sporulation, germination, and heat resistance. Journal of Biological Chemistry, 2018, 293 (47), pp.18040-18054. ⟨10.1074/jbc.RA118.004273⟩. ⟨hal-04374612⟩
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