Clostridioides difficile peptidoglycan modifications.

Curr Opin Microbiol

Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France. Electronic address:

Published: February 2022

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Peptidoglycan synthesis is an essential driver of bacterial growth and division. The final steps of this crucial process involve the activity of SEDS family glycosyltransferases that polymerize glycan strands and class B penicillin-binding protein (bPBP) transpeptidases that cross-link them. While most bacteria encode multiple bPBPs that perform specialized roles during specific cellular processes, some bPBPs can play redundant roles that are important for resistance against certain cell wall stresses.

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Article Synopsis
  • Clostridia produce Large Clostridial Glucosylating Toxins (LCGTs) that cause disease, but how these toxins are secreted is not well understood.
  • Researchers discovered that a holin-like protein is crucial for toxin secretion and explored the role of two potential lysins in this process in Clostridioides difficile strain M7404.
  • Analysis revealed that one of the lysins, M7404_02200, is essential for the non-lytic secretion of the toxins TcdA and TcdB, confirming its function as an active peptidoglycan amidase.
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Atomic structures of a bacteriocin targeting Gram-positive bacteria.

Nat Commun

August 2024

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.

Due to envelope differences between Gram-positive and Gram-negative bacteria, engineering precision bactericidal contractile nanomachines requires atomic-level understanding of their structures; however, only those killing Gram-negative bacteria are currently known. Here, we report the atomic structures of an engineered diffocin, a contractile syringe-like molecular machine that kills the Gram-positive bacterium Clostridioides difficile. Captured in one pre-contraction and two post-contraction states, each structure fashions six proteins in the bacteria-targeting baseplate, two proteins in the energy-storing trunk, and a collar linking the sheath with the membrane-penetrating tube.

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Article Synopsis
  • Most bacteria have a cell wall made of peptidoglycan, which consists of glycan strands linked by peptide cross-links, primarily classified as 4-3 and 3-3 based on their amino acid composition.
  • The majority of bacteria rely on 4-3 cross-links for survival, but in a specific intestinal pathogen, 3-3 cross-links are essential, making L,D-transpeptidases (LDTs) crucial for its viability.
  • This study identifies a new family of PG cross-linking enzymes, reveals the function of VanW domains, and highlights the potential of targeting LDTs for antibiotic development against this pathogen.
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Keratinicyclins and keratinimicins are recently discovered glycopeptide antibiotics. Keratinimicins show broad-spectrum activity against Gram-positive bacteria, while keratinicyclins form a new chemotype by virtue of an unusual oxazolidinone moiety and exhibit specific antibiosis against Clostridioides difficile. Here we report the mechanism of action of keratinicyclin B (KCB).

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