The cortex and peptidoglycan of Clostridioides difficile have been poorly investigated. This last decade, the interest increased because these two structures are highly modified and these modifications may be involved in antimicrobial resistance. For example, C. difficile peptidoglycan deacetylation was recently reported to be involved in lysozyme resistance. Modifications may also be important for spore cortex synthesis or spore germination, which is essential in C. difficile pathogenesis. As such, the enzymes responsible for modifications of the peptidoglycan and/or cortex could be new drug target candidates or used as anti-C. difficile agents, as seen for the CD11 autolysin. In this review, we focus on C. difficile peptidoglycan and cortex and compare their structures with those of other well studied bacteria.
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http://dx.doi.org/10.1016/j.mib.2021.11.010 | DOI Listing |
bioRxiv
September 2024
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
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.
View Article and Find Full Text PDFCommun Biol
August 2024
Department of Microbiology, Biomedicine Discovery Institute, Monash University, Clayton, 3800, Australia.
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.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2024
Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Nat Chem Biol
July 2024
Department of Chemistry, Princeton University, Princeton, NJ, USA.
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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