Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-3251

Sander, P; Rezwan, M; Walker, B; Rampini, S K; Kroppenstedt, R M; Ehlers, S; Keller, C; Keeble, J R; Hagemeier, M; Colston, M J; Springer, B; Böttger, E C (2004). Lipoprotein processing is required for virulence of Mycobacterium tuberculosis. Molecular Microbiology, 52(6):1543-1552.

[img] PDF - Registered users only
1MB

Abstract

Lipoproteins are a subgroup of secreted bacterial proteins characterized by a lipidated N-terminus, processing of which is mediated by the consecutive activity of prolipoprotein diacylglyceryl transferase (Lgt) and lipoprotein signal peptidase (LspA). The study of LspA function has been limited mainly to non-pathogenic microorganisms. To study a potential role for LspA in the pathogenesis of bacterial infections, we have disrupted lspA by allelic replacement in Mycobacterium tuberculosis, one of the world's most devastating pathogens. Despite the presence of an impermeable lipid outer layer, it was found that LspA was dispensable for growth under in vitro culture conditions. In contrast, the mutant was markedly attenuated in virulence models of tuberculosis. Our findings establish lipoprotein metabolism as a major virulence determinant of tuberculosis and define a role for lipoprotein processing in bacterial pathogenesis. In addition, these results hint at a promising new target for therapeutic intervention, as a highly specific inhibitor of bacterial lipoprotein signal peptidases is available.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
DDC:570 Life sciences; biology
610 Medicine & health
Date:2004
Deposited On:22 Aug 2008 12:27
Last Modified:27 Nov 2013 20:39
Publisher:Wiley-Blackwell
ISSN:0950-382X
Publisher DOI:10.1111/j.1365-2958.2004.04041.x
PubMed ID:15186407
Citations:Web of Science®. Times Cited: 72
Google Scholar™
Scopus®. Citation Count: 72

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page