Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/99893
Title: Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis
Authors: Normark, Staffan
Kandaswamy, Kumaravel
Liew, Tze Horng
Huston-Warren, Emily
Meyer-Hoffert, Ulf
Hultenby, Kjell
Henriques-Normark, Birgitta
Wang, Charles Y.
Schröder, Jens M.
Caparon, Michael G.
Hultgren, Scott J.
Kline, Kimberly A.
Keywords: DRNTU::Science::Biological sciences::Microbiology::Bacteria
Issue Date: 2013
Source: Kandaswamy, K., Liew, T. H., Wang, C. Y., Huston-Warren, E., Meyer-Hoffert, U., Hultenby, K., et al. (2013). Focal targeting by human β-defensin 2 disrupts localized virulence factor assembly sites in Enterococcus faecalis. Proceedings of the National Academy of Sciences of the United States of America, 110(50), 20230-20235.
Series/Report no.: Proceedings of the National Academy of Sciences of the United States of America
Abstract: Virulence factor secretion and assembly occurs at spatially restricted foci in some Gram-positive bacteria. Given the essentiality of the general secretion pathway in bacteria and the contribution of virulence factors to disease progression, the foci that coordinate these processes are attractive antimicrobial targets. In this study, we show in Enterococcus faecalis that SecA and Sortase A, required for the attachment of virulence factors to the cell wall, localize to discrete domains near the septum or nascent septal site as the bacteria proceed through the cell cycle. We also demonstrate that cationic human β-defensins interact with E. faecalis at discrete septal foci, and this exposure disrupts sites of localized secretion and sorting. Modification of anionic lipids by multiple peptide resistance factor, a protein that confers antimicrobial peptide resistance by electrostatic repulsion, renders E. faecalis more resistant to killing by defensins and less susceptible to focal targeting by the cationic antimicrobial peptides. These data suggest a paradigm in which focal targeting by antimicrobial peptides is linked to their killing efficiency and to disruption of virulence factor assembly.
URI: https://hdl.handle.net/10356/99893
http://hdl.handle.net/10220/18581
DOI: 10.1073/pnas.1319066110
Schools: School of Biological Sciences 
Organisations: Singapore Centre for Environmental Life Sciences Engineering
Rights: © 2013 The Authors. This paper was published in Proceedings of the National Academy of Sciences of the United States of America and is made available as an electronic reprint (preprint) with permission of the authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1073/pnas.1319066110]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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