Chemical Probes of Surface Layer Biogenesis in Clostridium difficile

Autor:	Edward W. Tate, Robert P. Fagan, William P. Heal, Elisabeth M. Storck, Claire Janoir, T. H. Tam Dang, Neil F. Fairweather, Lucia de la Riva
Rok vydání:	2010
Předmět:	biology Clostridioides difficile General Medicine Clostridium difficile biology.organism_classification Cleavage (embryo) Biochemistry Cysteine protease Clostridia Cysteine Endopeptidases Bacterial Proteins In vivo Host-Pathogen Interactions Humans Molecular Medicine Bacteria Biogenesis
Zdroj:	ACS Chemical Biology. 5:279-285
ISSN:	1554-8937 1554-8929
Popis:	Clostridium difficile, a leading cause of hospital-acquired infection, possesses a dense surface layer (S-layer) that mediates host-pathogen interactions. The key structural components of the S-layer result from proteolytic cleavage of a precursor protein, SlpA, into high- and low-molecular-weight components. Here we report the discovery and optimization of the first inhibitors of this process in live bacteria and their application for probing S-layer processing. We also describe the design and in vivo application of activity-based probes that identify the protein Cwp84 as the cysteine protease that mediates SlpA cleavage. This work provides novel chemical tools for the analysis of S-layer biogenesis and for the potential identification of novel drug targets within clostridia and related bacterial pathogens.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a60656b28fd3b2c9db71ae703e1bd5d4 https://doi.org/10.1021/cb9002859 Zobrazit plný text záznamu