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Chemical probes of surface layer biogenesis in Clostridium difficile.

Abstract：

: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.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Dang TH,de la Riva L,Fagan RP,Storck EM,Heal WP,Janoir C,Fairweather NF,Tate EW

doi

10.1021/cb9002859

subject

Has Abstract

pub_date

2010-03-19 00:00:00

pages

279-85

issue

3

eissn

1554-8929

issn

1554-8937

journal_volume

5

pub_type

杂志文章

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